Dissertations / Theses: 'Binding sites (Biochemistry) Ligand binding (Biochemistry)'

1

Olsen, Gregory L. "Magnetic resonance studies of binding site structure and dynamics in TAR RNA /." Thesis, Connect to this title online; UW restricted, 2007. http://hdl.handle.net/1773/8581.

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Hauser, Melanie R. "Selective calcium binding by alpha-hydoxyketones and alpha-hydroxyamides /." view abstract or download file of text, 2006. http://proquest.umi.com/pqdweb?did=1251854561&sid=3&Fmt=2&clientId=11238&RQT=309&VName=PQD.

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Thesis (Ph. D.)--University of Oregon, 2006.
Typescript. Includes vita and abstract. Includes bibliographical references (leaves 115 - 121). Also available for download via the World Wide Web; free to University of Oregon users.

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3

Prasannan, Charulata Bhaskaran. "Modulation of restriction enzyme PvuII activity by metal ion cofactors." Diss., St. Louis, Mo. : University of Missouri--St. Louis, 2009. http://etd.umsl.edu/r4461.

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4

Penkler, David Lawrence. "In silico analysis of human Hsp90 for the identification of novel anti-cancer drug target sites and natural compound inhibitors." Thesis, Rhodes University, 2015. http://hdl.handle.net/10962/d1018938.

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The 90-KDa heat shock protein (Hsp90) is part of the molecular chaperone family, and as such it is involved in the regulation of protein homeostasis within cells. Specifically, Hsp90 aids in the folding of nascent proteins and re-folding of denatured proteins. It also plays an important role in the prevention of protein aggregation. Hsp90’s functionality is attributed to its several staged, multi-conformational ATPase cycle, in which associated client proteins are bound and released. Hsp90 is known to be associated with a wide array of client proteins, some of which are thought to be involved in multiple oncogenic processes. Indeed Hsp90 is known to be directly involved in perpetuating the stability and function of multiple mutated, chimeric and over-expressed signalling proteins that are known to promote the growth and survival of cancer cells. Hsp90 inhibitors are thus thought to be promising therapeutic agents for cancer treatment. A lack of a 3D structure of human Hsp90 however has restricted Hsp90 inhibitor development in large to in vivo investigations. This study, aims to investigate and calculate hypothetical homology models of the full human Hsp90 protein, and to probe these structural models for novel drug target sites using several in silico techniques. A multi-template homology modelling methodology was developed and in conjunction with protein-protein docking techniques, two functionally important human Hsp90 structural models were calculated; the nucleotide free “v-like” open and nucleotide bound closed conformations. Based on the conservation of ligand binding, virtual screening experiments conducted on both models using 316 natural compounds indigenous to South Africa, revealed three novel putative target sites. Two binding pockets in close association with important Hsp90-Hop interaction residues and a single binding pocket on the dimerization interface in the C-terminal domain. Targeted molecular docking experiments at these sites revealed two compounds (721395-11-5 and 264624-39-7) as putative inhibitors, both showing strong binding affinities for at least one of the three investigated target sites. Furthermore both compounds were found to only violate one Lipinski’s rules, suggesting their potential as candidates for further drug development. The combined work described here provides a putative platform for the development of next generation inhibitors of human Hsp90.

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Carlsson, Jens. "Challenges in Computational Biochemistry: Solvation and Ligand Binding." Doctoral thesis, Uppsala University, Department of Cell and Molecular Biology, 2008. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-8738.

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Accurate calculations of free energies for molecular association and solvation are important for the understanding of biochemical processes, and are useful in many pharmaceutical applications. In this thesis, molecular dynamics (MD) simulations are used to calculate thermodynamic properties for solvation and ligand binding.

The thermodynamic integration technique is used to calculate pK_a values for three aspartic acid residues in two different proteins. MD simulations are carried out in explicit and Generalized-Born continuum solvent. The calculated pK_a values are in qualitative agreement with experiment in both cases. A combination of MD simulations and a continuum electrostatics method is applied to examine pK_a shifts in wild-type and mutant epoxide hydrolase. The calculated pK_a values support a model that can explain some of the pH dependent properties of this enzyme.

Development of the linear interaction energy (LIE) method for calculating solvation and binding free energies is presented. A new model for estimating the electrostatic term in the LIE method is derived and is shown to reproduce experimental free energies of hydration. An LIE method based on a continuum solvent representation is also developed and it is shown to reproduce binding free energies for inhibitors of a malaria enzyme. The possibility of using a combination of docking, MD and the LIE method to predict binding affinities for large datasets of ligands is also investigated. Good agreement with experiment is found for a set of non-nucleoside inhibitors of HIV-1 reverse transcriptase.

Approaches for decomposing solvation and binding free energies into enthalpic and entropic components are also examined. Methods for calculating the translational and rotational binding entropies for a ligand are presented. The possibility to calculate ion hydration free energies and entropies for alkali metal ions by using rigorous free energy techniques is also investigated and the results agree well with experimental data.

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Ridd, Thomas Ian. "Reactions and ligand binding properties of cytochrome P450." Thesis, University of Surrey, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.308553.

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Jones, Marc. "Folate binding protein : partial characterisation of bovine milk folate binding protein, includings its ligand binding /." [St. Lucia, Qld], 2004. http://www.library.uq.edu.au/pdfserve.php?image=thesisabs/absthe18263.pdf.

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8

Jiang, Tao. "Characterisation of recombinant aryl hydrocarbon receptor ligand binding domain." Thesis, University of Nottingham, 2004. http://eprints.nottingham.ac.uk/10401/.

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Aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor, which mediates the toxicity of dioxin and related compounds, and has an important role in development. However, a structural basis for ligand binding to the AhR remains unclear and the study was hindered by the low abundance and inherited instability of the AhR. Based on a previously defined minimal ligand-binding domain (LBD, residues 230-421), in the present study a series of truncated LBD constructs were created and expressed in insect cells (Sf9) using a baculovirus expression system. An antibody was produced to analyze the expressed. The antisera can detect as low as 0.3ng of AhR LBD from cytosol of Sf9. An in vitro [3H]TCDD binding assay was developed to characterized the expressed LBD. The assay yielded an estimate for the KD of C57Bl/6 mouse liver binding at 1.4nM. The present expression system yields soluble AhR LBD protein at ~0.15% of cytosol protein. Supplementation of the Sf9 culture medium with additional glucose resulted in an increase in the amount of soluble AhR, due to an increase in intracellular ATP level. However, cotransfection of LBD with hsp90 interaction protein p23 made no substantial change in the amount of cytosolic AhR. The soluble recombinant LBD retains functionality in the form of specific binding to dioxin, and its thermal stability was indistinguishable from that of mouse liver. However the ligand-binding activity of LBD was molybdate dependent, indicating a weaker association of mouse AhR LBD with Sf9 hsp90. A differential effect of Triton X-100 on the recombinant AhR LBD and native AhR also suggests that the interaction between AhR and Sf9 hsp90 is less stable. The study refined the minimal LBD to a region of 125 amino acids, which should be amenable for structural studies of the LBD.

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Ayre, Elizabeth Anne. "The characterization, localization and physiological regulation of [125I] iodomelatonin binding sites in the gonads." Thesis, [Hong Kong : University of Hong Kong], 1993. http://sunzi.lib.hku.hk/hkuto/record.jsp?B13554177.

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McFail-Isom, Lori. "Effects of ligand binding, coordinate error and ion binding on nucleic acid structure and conformation." Diss., Georgia Institute of Technology, 1998. http://hdl.handle.net/1853/30735.

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Wade, R. C. "Ligand-macromolecule interactions." Thesis, University of Oxford, 1988. http://ora.ox.ac.uk/objects/uuid:576ce119-6a93-4eb0-a7e4-1f2513736dbd.

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The optimisation of ligand-macromolecule interactions is fundamental to the design of therapeutic agents. The GRID method is a procedure for determining energetically favourable ligand binding sites on molecules of known structure using an empirical energy potential. In this thesis, it has been extended, tested, and then applied to the design of anti-influenza agents. In the GRID method, the energy of a hydrogen-bond is determined by a function which is dependent on the length of the hydrogen-bond, its orientation at the hydrogen-bond donor and acceptor atoms, and the chemical nature of these atoms. This function has been formulated in order to reproduce experimental observations of hydrogen-bond geometries. The reorientation of hydrogen atoms and lone-pair orbitals on the formation of hydrogen-bonds is calculated analytically. The experimentally observed water structures of crystals of four biological molecules have been used as model systems for testing the GRID method. It has been shown that the location of well-ordered waters can be predicted accurately. The ability of the GRID method to assist in the assignment of water sites during crystallographic refinement has been demonstrated. It has also been shown that waters in the active site of an enzyme may be both stabilized and displaced by a bound substrate. Ligands have been designed to block the highly conserved host cell receptor site of the influenza virus haemagglutinin in order to prevent the attachment of the virus to the host cells. The protein was mapped energetically by program GRID and specific ligand binding sites were identified. Ligands, which exploited these binding sites, were then designed using computer graphics and energy minimization techniques. Some of the designed ligands were peptides and these were synthesised and assayed. Preliminary results indicate that they may possess anti-influenza activity.

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Fong, Desiree Ho-Chi. "Structural basis of ligand binding to 3',5'' -aminoglycoside O-phosphotransferase type IIIa." Thesis, McGill University, 2006. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=100364.

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3',5"-aminoglycoside O-phosphotransferase type IIIa (APH(3')-IIIa) is an enzyme produced by pathogenic Gram-positive bacteria such as Enterococci and Staphylococci. It is capable of conferring resistance to a broad range of clinically important aminoglycoside antibiotics via the ATP-dependent addition of a phosphate to specific hydroxyl groups on the drug. The phosphorylated amino-glycoside loses its toxic effects due to reduced affinity for its target, the A-site of 30S ribosome. Crystal structures of several ternary complexes have been elucidated in an effort to understand the promiscuity of substrate recognition by APH(3')-IIIa. They are APH(3')-IIIa bound with ADP and kanamycin or neomycin to resolutions of 2.4 A and 2.7 A, respectively, as well as the structures of APH(3')-IIIa bound with AMPPNP and butirosin or 5"-monophosphorylated butirosin to resolutions of 2.4 A and 2.7 A, respectively. These structures reveal that the basis for this enzyme's broad substrate spectrum is the presence of a flexible antibiotic-binding loop and a versatile antibiotic-binding pocket composed of three sub-sites. A comparison of the A-site of the bacterial ribosome and APH(3')-IIIa shows a high degree of similarity in the pattern of hydrogen bonds to the aminoglycoside. However, they differ in their van der Waals interactions with the substrate, suggesting a potential strategy for the design of novel antibiotics and adjuvants. Another strategy for overcoming antibiotic resistance resulting from the effects of APH(3')-IIIa is the development of inhibitors that target the nucleotide-binding pocket of the enzyme. It has been shown that APH(3')-IIIa possess striking structural and functional similarity to eukaryotic protein kinases (ePKs). In particular, APH(3')-IIIa is sensitive to several ATP-competitive protein kinase inhibitors. To aid the design of ligands with high specificity to the nucleotide-binding pocket of APH(3')-IIIa, the crystal structure of APH(3')-IIIa bound with CKI-7, a casein kinase 1 inhibitor, has also been determined to 2.5 A resolution. Distinct features can be identified upon detailed comparisons between CKI-7-bound and nucleotide-bound APH(3')-IIIa and isoquinolinesulfonainide-bound ePKs. It is hoped that these results will contribute to the design of compounds that will allow aminoglycoside antibiotics to remain useful components of the antibacterial armamentarium.

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Cubberley, Rachel Reita. "The cofactor and substrate binding sites of human inducible nitric oxide synthase." Thesis, University of Warwick, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.390033.

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14

陳雅莉 and Nga-li Celia Chan. "An examination of homeodomains and their binding sites." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2001. http://hub.hku.hk/bib/B42575850.

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Chan, Nga-li Celia. "An examination of homeodomains and their binding sites." Click to view the E-thesis via HKUTO, 2001. http://sunzi.lib.hku.hk/hkuto/record/B42575850.

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Goodarzi, Jim Pasha. "Biopolymer dynamics : end-to-end looping and large ligand binding /." view abstract or download file of text, 2004. http://wwwlib.umi.com/cr/uoregon/fullcit?p3153787.

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Thesis (Ph. D.)--University of Oregon, 2004.
Typescript. Includes vita and abstract. Includes bibliographical references (leaves 216-223). Also available for download via the World Wide Web; free to University of Oregon users.

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17

Guo, Guanlun. "Stereo-selective binding of enantiomeric ligands in PPAR[gamma] : a molecular modeling study." HKBU Institutional Repository, 2013. http://repository.hkbu.edu.hk/etd_ra/1516.

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18

Parker, Matthew W. "Molecular Mechanisms of Neuropilin-Ligand Binding." UKnowledge, 2014. http://uknowledge.uky.edu/biochem_etds/15.

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Neuropilin (Nrp) is an essential cell surface receptor with dual functionality in the cardiovascular and nervous systems. The first identified Nrp-ligand family was the Semaphorin-3 (Sema3) family of axon repulsion molecules. Subsequently, Nrp was found to serve as a receptor for the vascular endothelial growth factor (VEGF) family of pro-angiogenic cytokines. In addition to its physiological role, VEGF signaling via Nrp directly contributes to cancer stemness, growth, and metastasis. Thus, the Nrp/VEGF signaling axis is a promising anti-cancer therapeutic target. Interestingly, it has recently been shown that Sema3 and VEGF are functionally opposed to one another, with Sema3 possessing potent endogenous anti-angiogenic activity and VEGF serving as an attractive cue for neuronal axons. We hypothesized that direct competition for an overlapping binding site within the Nrp extracellular domain may explain the observed functional competition between VEGF and Sema3. To test this hypothesis we have separately investigated the mechanisms of VEGF and Sema3 binding to Nrp. Utilizing structural biology coupled with biophysics and biochemistry we have identified both distinct and common mechanisms that facilitate the interaction between Nrp and these two ligand families. Specifically, we have identified an Nrp binding pocket to which these ligands competitively bind. The Sema3 family uniquely requires proteolytic activation in order to engage this overlapping binding site. These findings provide critical mechanistic insight into VEGF and Sema3 mediated physiology. Additionally, these data have informed the development of small molecules, peptides, and soluble receptor fragments that function as potent and selective inhibitors of VEGF/Nrp binding with exciting therapeutic potential for treating cancer.

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Mayevu, Ntateko Merriam Immogen. "The contribution of His7.36(305) of the GnRH receptor to ligand binding and receptor activation." Master's thesis, University of Cape Town, 2004. http://hdl.handle.net/11427/3141.

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Bibliography: leaves 88-104.
The current study was perfonned to give insights into the role of individual amino acid residues of both the GnRH receptor and the GnRH ligand in receptor function. A His7.36(3o5) residue on transmembrane helix seven of the GnRH receptor was investigated for its contribution to the overall function of the receptor.

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Nadassy, Katalin. "Molecular recognition by proteins : structural features of zinc and protein-nucleic acid binding sites." Thesis, University of Stirling, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.341227.

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李保能 and Po-nung Peter Lee. "Melatonin and 2-[125I]iodomelatonin binding sites in the gastrointestinal tract." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 1993. http://hub.hku.hk/bib/B31233673.

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Tedeschi, Frank A. Tedeschi. "IDENTIFICATION OF CELLULAR RNA BINDING SITES OF DEAD-BOX HELICASES." Case Western Reserve University School of Graduate Studies / OhioLINK, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=case1531217057171378.

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23

Watt, Terry J. "Engineering a better receptor characterization of retinoid x receptor alpha and functional variants /." Diss., Atlanta, Ga. : Georgia Institute of Technology, 2007. http://hdl.handle.net/1853/26647.

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Thesis (Ph. D.)--Chemistry and Biochemistry, Georgia Institute of Technology, 2008.
Committee Chair: Doyle, Donald; Committee Member: Bommarius, Andreas; Committee Member: Harvey, Stephen; Committee Member: Hud, Nicholas; Committee Member: Kubanek, Julia. Part of the SMARTech Electronic Thesis and Dissertation Collection.

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Taylor, Paul Brian. "Characterising the Notch-ligand binding interaction, and its modulation by glycosylation." Thesis, University of Oxford, 2012. http://ora.ox.ac.uk/objects/uuid:b6867987-f789-4da2-9444-992e481bb3e6.

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The Notch signalling pathway is universally conserved in all metazoan species, and is involved in many aspects of cell fate determination and tissue homeostasis, during development and in adult organisms. Several developmental diseases are associated with defective Notch signalling, and the Notch pathway has been implicated in a growing number of cancers. The Notch signalling pathway requires direct cell-cell contact for ligand binding and receptor activation to occur. Specific domains within the Notch receptors and ligands have been identified as necessary for the interaction to take place, and a series of enzymes are known to regulate Notch signalling via glycosylation. Other domains beyond the minimal ligand binding region of the Notch receptor are also known to influence binding. The aim of this study was to characterise the molecular basis for ligand binding by the Notch receptor, and how this is regulated by glycosylation. The effects on ligand binding of specific amino acid substitutions and sugar modifications were tested using prokaryotically -expressed proteins, and a series of constructs containing additional domains N-terminal of the ligand binding region was produced prokaryotically and eukaryotically to test how additional domains might affect ligand binding. Binding was assessed by a flow cytometry-based binding assay and by SPR in order to investigate how particular modifications affected ligand binding. These assays indicated that an evolutionarily-conserved hydrophobic site exists within the central β-sheet of EGF12 in the Notch receptor that is directly adjacent to the O-fucosylation site within this domain. The GlcNAc-fucose disaccharide modification at this position was found to increase binding of hNotch1 to both Jagged1 and DLL4. Additional EGF domains N-terminal to the ligand binding region showed opposite effects on binding to these two ligand classes, suggesting that the precise mode of binding may vary slightly between different Notch ligands.

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Tan, Chik Kaw. "Development of a ligand-receptor binding assay for characterizing AVP receptors in isolated rat kidney tubules." Thesis, Keele University, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.262383.

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26

Cui, Donghui. "Investigation of the axial binding of phosphrus (sic) ligands to tetraphenylporphinato iron (II)." FIU Digital Commons, 1992. http://digitalcommons.fiu.edu/etd/2682.

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Phosphines and phosphites have been investigated as ligands to tetraphenylporphinato iron(II) (FeTPP) by spectrophotometric titration in tetrahydrofuran. A least squares method for determination of the equilibrium constants K1 and K2 (K1 and K2 correspond to the sequential binding constants for the formation of FeTPPL and FeTPPL2, respectively) was developed. This method eliminates the errors associated with fundamental assumptions intrinsic to the more conventional Hill plot. The visible spectrum of the 5-coordinate complex, FeTPPL, was also determined for each ligand. The equilibrium constants obtained are: {L(logK1, logK 2)}, PMe3 (5.53, 4.60); PEt3 (5.61, 4.30); P(n- Bu)3 (6.13, 5.02); P(OEt)3 (3.87, 2.82); P(O-i-Pr)3 (3.28, 1.13). The equilibrium constants are dependent upon steric bulk, σ-basicity and π-acidity.

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Kandala, Srikanth Richmond Michael G. "Synthesis and characterization of diphosphine ligands and diphosphine substituted osmium and ruthenium clusters." [Denton, Tex.] : University of North Texas, 2007. http://digital.library.unt.edu/permalink/meta-dc-3955.

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28

Peiser, Leanne. "The role of the macrophage scavenger receptor in host defence." Thesis, University of Oxford, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.393470.

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Xu, Rong. "The effects of structural modifications on sigma receptor binding." Diss., Columbia, Mo. : University of Missouri-Columbia, 2007. http://hdl.handle.net/10355/4742.

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Thesis (Ph. D.)--University of Missouri-Columbia, 2007.
The entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file. Title from title screen of research.pdf file (viewed on December 18, 2007) Vita. Includes bibliographical references.

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Lim, Hong-Sheng. "Ligand binding and signalling by the T cell antigen receptor and CD28." Thesis, University of Oxford, 2014. http://ora.ox.ac.uk/objects/uuid:17bb3aa2-02fd-4f48-a4ad-1dd5c6ee67aa.

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Successful T cell activation depends on the recognition of antigenic peptides in the context of a Major Histocompatibility Complex molecule (pMHC) by the T cell antigen receptor (TCR), together with additional signals from co-stimulatory receptors such as CD28. Despite their importance, a thorough understanding of how TCR-pMHC binding properties relate to T cell functional responses remains unclear. In addition, there are no consensuses to the exact mechanism leading to CD28 receptor triggering. Activation of CD28 is dependent on the phosphorylation of key tyrosine residues within its cytoplasmic domain by Src family kinases. Just like the TCRs, CD28 receptors are susceptible to perturbations of the local kinase: phosphatase ratio. The K-S model postulates that upon ligand engagement, large RPTPs such as CD45 are segregated from the area of close contact, resulting in increased relative kinase concentration and CD28 receptor triggering. This hypothesis was tested in chapter 3, where elongated forms of CD80 were examined for their ability to costimulate primary T cells. CD28 costimulation was indeed diminished and there was reduced CD45 segregation from the elongated CD80 molecules. Additionally, CD28 habouring key Y170F tyrosine mutations were less susceptible to CD28 signal abrogation by elongated CD80 molecules. Interestingly, elongated CD80 molecules remained much less effective in mediating costimulation even when pMHC molecules were also elongated, suggesting that TCR-pMHC and CD28-CD80 size matching is not critical for costimulation. Despite the well-documented MHC-restriction requirement for TCR recognition, the relative energetic contributions of peptide versus MHC in TCR-pMHC interactions remain elusive. To address this question, the energetic footprints of four TCRs (1G4, JM22, A6 and G10) to HLA-A2 were determined via systematic alanine scanning mutagenesis on the HLA-A2 heavy chain in chapter 4. By targeting exclusive TCR contacting residues on the MHC, we conservatively estimate the contribution of MHCs for the four TCRs to range from 15% to over 70%. Several models have been formulated in an attempt to relate TCR-pMHC binding properties to T cell activation. Validity of the models was tested in chapter 5 using a supra-physiological TCR. By mutating key residues within the cognate pMHC, we generated a panel of TCR-pMHC with affinities that varies up to 105-fold. These reagents were used to stimulate Jurkat and primary T cells transduced with the supra-physiological TCR. Results in the Jurkat T cell system demonstrated the presence of an optimal off-rate (k_off) for TCR-pMHC interaction at low concentrations of pMHC concentration. The results argue against affinity models and the basic kinetic proofreading model for T cell activation.

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Paulo, Joao A. "Exploring intramolecular and intermolecular interactions of -bungarotoxin binding proteins." View abstract/electronic edition; access limited to Brown University users, 2008. http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&res_dat=xri:pqdiss&rft_dat=xri:pqdiss:3318348.

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Usoh, George. "Biochemical and pharmacological characterisations of L-glutamate and phenylcyclidine binding sites in insect central nervous system." Thesis, University of Nottingham, 1990. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.238232.

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Xiong, Wen-cheng 1962. "Characterization of a [³H]-5-hydroxytryptamine binding site in rabbit brain." Thesis, The University of Arizona, 1989. http://hdl.handle.net/10150/291537.

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In the present study non-5-HT₁(A)/non-5-HT₁(C) binding sites in the rabbit caudate nucleus (CN) were examined to determine if they might be identical to the recently discovered 5-HT₁(D) sites in the bovine CN. The characterizations were carried out measuring high-affinity [³H]5-HT binding under conditions where 5-HT₁(A) and 5-HT₁(C) sites were pharmacologically masked in both tissues. Comparison of the pharmacologic profiles of the bovine 5-HT₁(D) and rabbit non-5-HT₁(A)/non-5-HT₁(C) sites revealed similarities, but showed distinct differences. [³H]5-HT binding in the bovine CN was significantly more sensitive to inhibition by GTP than was [³H]5-HT binding in the rabbit CN, and this effect was differentially sensitive to calcium and other divalent cations (i.e., Mg²⁺, Mn²+)⁺in the two tissues. [³H]5-HT binding in the bovine CN was significantly more sensitive to inhibition by NEM than it was in the rabbit CN. Thus, it may be concluded that the non-5-HT₁(A)/non-5-HT₁(C) [³H]5-HT binding sites in rabbit CN are distinct from those in the bovine CN, and we propose that they be tentatively identified as 5-HT₁(R) to distinguish them from the 5-HT₁(D) site.

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Garduño, Bertha Veronića. "Cbf1 regulates chromatin remodelling of the Saccharomyces cerevisiae genome at multiple binding sites." Thesis, University of Oxford, 1999. http://ora.ox.ac.uk/objects/uuid:be76ba21-1336-4ac8-9da3-918fd58d5908.

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The centromere binding factor 1, Cbf1, of Saccharomyces cerevisiae is a bHLH/ZIP protein which has been described as a determinant of specific chromatin structures and as a tethering factor for activators of transcription at the promoters of genes of the Methionine Biosynthesis Pathway. Deletion mutants show various phenotypes, among them methionine auxotrophy, an increased rate of chromosome loss, modifications in the growth rate and modification of the chromatin structure at MET genes. Meiosis competence also becomes greatly reduced in cbf1 cells. The sequence motif (RTCACRTG) to which Cbf1p binds is found at multiple loci through the yeast genome. This thesis shows that the chromatin structure is reorganised at multiple Cbf1p binding sites in vivo, when yeast cells are starved to enter meiosis. Extensive remodelling occurs at the MET16, MET17(25), DRS2 and GDH3 loci and at the YAL060W open reading frame, as detected by in vivo digestion of chromatin with micrococcal nuclease and indirect end-labelling. The same kind of analysis showed that the remodelling of chromatin at Cbf1p binding sites is not specific for meiosis, it occurs also in similarly starved haploid cells. The lack of methionine is a key trigger of these changes. This reorganisation of chromatin is dependent on Cbf1p, since starved cbf1 cells do not display any modification in nuclease accessibility patterns at or around Cbf1p binding sites. Mutational analysis revealed that a negative charge at a putative phosphorylation site (serine residue 226) and the DNA-bindmg activity of Cbf1p are both required for the chromatin reorganisation to occur in response to starvation. CBF1 mutants which do not reorganise chromatin were also shown to be unable to enter meiosis, suggesting that the remodelling of chromatin at multiple Cbf1p binding sites may be required to enter pre-meiotic DNA replication, since such cells arrest before the initiation of this process. In summary, the results presented in this thesis are compatible with a model in which Cbf1p plays an active role as part of a mechanism sensing the nutrient availability and regulates the reorganisation of chromatin, at multiple loci through the yeast genome, in response to starvation conditions.

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Sekharan, Monica R. "Structural studies of the cGMP-binding GAF domain of PDE5A /." Thesis, Connect to this title online; UW restricted, 2004. http://hdl.handle.net/1773/8502.

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Nguyen, Nhung Phuong. "Axial ligand mutant H229A /." unrestricted, 2007. http://etd.gsu.edu/theses/available/etd-08082008-134926/.

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Thesis (honors)--Georgia State University, 2007.
Title from file title page. Under the direction of Dabney White Dixon. Electronic text (88 p. : col. ill.) : digital, PDF file. Description based on contents viewed Sept. 30, 2008. Includes bibliographical references (p. 46-47).

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37

Tolentino, Timothy P. "Measuring ligand diffusivity and receptor binding kinetics within a cell membrane contact area." Thesis, Georgia Institute of Technology, 2001. http://hdl.handle.net/1853/20297.

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38

Ley, Nathan Benjamin. "Investigations into fragment ligand binding using quantitative STD and WaterLOGSY NMR spectroscopy." Thesis, University of Kent, 2015. https://kar.kent.ac.uk/50197/.

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Ligand-observed NMR spectroscopy is frequently employed in early-stage drug discovery, often as an initial screen to narrow the field of potential drug-like molecules. However, its use is limited to this early stage. More information regarding binding mode can be extracted from these experiments via quantification, and this should help extend the remit of these experiments beyond simple screening functions. Initially, it was shown that the amount of signal that could be produced from an STD NMR experiment could be dramatically increased by careful consideration of the selective saturation pulse. By systematically shortening the Gaussian pulse and positioning it at specific offset positions, it was shown that these dramatic increases in signal are genuine and need not result in false positives. Quantitative STD NMR spectroscopy as applied to Hsp90 and a series of small fragment ligands provided evidence to suggest that the precise inter-atomic distances between a protein and ligand within a crystal structure correlate with both initial rates of STD build up, and T1-adjusted STD values. This precise correlation has implications for chemotype clustering and initial binding mode selection, something which should be useful in the absence of a crystal structure. Taking the same quantitative principles and applying to LOGSY experiments elucidated another, discrete property of protein-ligand binding. Examining the ‘LOGSY difference’ signal for protons of a ligand allows us to see what protons are in close proximity to conserved, bound water at the protein-ligand binding interface. This is fundamentally different to the information gained from STD experiments. Applying the insights to a protein of a different nature, Ras, it was shown that quantitative STD can be applied to proteins of both different size and structure. Furthermore, more evidence was acquired to suggest that conserved, bound water in the binding site really is responsible for generating LOGSY signal. In the absence of these molecules, as in Ras, proximity of a proton to an exchangeable tends to dominate. In addition we were able to show that these quantitative methods can be used together to help eliminate incorrect computationally generated docking poses. The work presented in this thesis provides evidence for the advantages of STD and LOGSY NMR spectroscopy in fragment-based drug discovery. The information that can be extracted from relatively simple ligand-observed NMR experiments should be used to provide more evidence at an earlier stage of the drug discovery process, hopefully reducing late-stage attrition and helping us get to the therapeutic drug molecules we need a little more quickly.

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Khawaja, Xavier. "Central and peripheral opioid peptides and their receptor binding sites : role in insulin secretion and glucose homeostasis." Thesis, University of Sussex, 1987. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.328582.

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Bascoy, Marta L. "N-acetoxy-N-acetyl-2-aminofluorene binding sites on [phi] X174 and SV40." FIU Digital Commons, 1991. http://digitalcommons.fiu.edu/etd/1429.

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Restriction enzyme inhibition and lambda exonuclease studies indicate that carcinogen N-acetoxy-N-acetyl-2 aminofluorene (AAAF) binds to sequences on ɸX174 RF and SV40 plasmids DNA that are similar to the eight preferred binding sites previously located on pBR 322. Both DNAs were digested with enzyme Hinf I and resultant fragments 32P end-labeled. Labeled fragments were reacted with the carcinogen to give one to sixteen bound moieties per DNA. Fragments were isolated and restriccion enzyme and lambda exonuclease inhibition assays were performed. Inhibition detected occurred at selected sites and was not specific for a certain enzyme or certain size of recognition sequence. Results of these assays allow mapping of the location of high affinity binding sites of the carcinogen on both DNAs. All sites have common sequence elements: the presence of either the sequence T(G/C)TT(G/C) or the sequence T(G/C) CTT(G/C).

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Engelhart, Aaron Edward. "Nucleic acid assembly, polymerization, and ligand binding." Diss., Georgia Institute of Technology, 2012. http://hdl.handle.net/1853/45979.

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In the past 30 years, the discovery of capabilities of nucleic acids far beyond their well-known information-bearing capacity has profoundly influenced our understanding of these polymers. The discovery by the Cech and Altman labs that nucleic acids could perform catalytic functions, coupled with the Gold and Szostak groups’ demonstration of the de novo evolution of nucleic acids that bind arbitrary ligands, has resulted in a proliferation of newfound roles for these molecules. Nucleic acids have found utility in both engineered systems, such as aptamer therapeutics, as well as in newly appreciated roles in extant organisms, such as riboswitches. As a result of these discoveries, many have pondered the potential importance of the dual (catalytic and informational) roles of nucleic acids in early evolution. A high-yielding synthetic route for the nonenzymatic polymerization of nucleic acids, based on the aqueous self-assembly of their components, would provide a powerful tool in nucleic acid chemistry, with potential utility in prebiotic and contemporary nucleic acid systems alike – however, such a route remains elusive. In this thesis, I describe several steps towards such a synthetic route. In these systems, a nucleic-acid binding ligand drives the assembly of short DNA and RNA duplexes, promoting the production of long nucleic acid polymers, while suppressing the production of short, cyclic species. Additionally, the use of a reversible covalent linkage allows for the production of long polymers, as well as the incorporation of previously cyclized products into these polymers. I also report several explorations of novel base pairings, nucleic acid-ligand interactions, and nucleic acid-ion interactions that have informed our studies of self-assembling nucleic acid systems.

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42

Broadhurst, A. M. "Alpha-2-adrenoreceptor binding sites in rat cortex : their characterisation and subcellular distribution by means of 3H-rauwolscine binding and preliminary experiments into the further elucidation of their autoreceptor function." Thesis, University of Southampton, 1987. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.303710.

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Ewing, Robyn. "Analysis of the subcellular trafficking of the glucocorticoid receptor and properties of the ligand binding domain." Thesis, University of Ottawa (Canada), 2008. http://hdl.handle.net/10393/27979.

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The glucocorticoid receptor (GR) is a ligand dependent transcription factor and member of the nuclear receptor superfamily. Nuclear import and export of transcription factors is accomplished through nuclear localization signals (NLS) and nuclear export signals (NES), respectively. We have determined that L687 and L690 of rat GR are necessary for the characteristically slow nuclear export of GR and may be included in the signal sequence responsible for directing post-agonist withdrawn GR from the nucleus to the cytoplasm. We also suggest that L687 and L689 of rat GR are required for efficient NL2-mediated nuclear translocation. Substitutions L687A and L689A mildly affect steroid binding and steroid off-rate, yet significantly increase the concentration of steroid required for inducing nuclear import of naive GR. When introduced into GRNL1-, these substitutions compromise the receptor's ability to transfer to the nucleus, suggesting they partially abrogate NL2 activity. We have also observed that NL1-dependent transfer does not begin until 10 -7M steroid, demonstrating that NL2 is the primary physiological mediator of GR nuclear import.

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Scott, Daniel James. "Characterizing the extracellular domains of the relaxin and INSL3 receptors, LGR7 and LGR8 /." Connect to thesis, 2006. http://eprints.unimelb.edu.au/archive/00003252.

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何振華 and Chun-wah Ho. "Study on osmium and manganese complexes of chiral binaphthylic tetradentate ligands and their application to asymmetric epoxidationof alkenes." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 1994. http://hub.hku.hk/bib/B31233570.

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Engle, Keary Mark. "Ligand-accelerated catalysis in palladium(II)-mediated C-H functionalisation ; Hydrogen bonding effects on the reactivity of fluoride anion." Thesis, University of Oxford, 2013. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.711664.

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Wu, Guanmin Richmond Michael G. "Synthesis characterization, and kinetics of isomerization, C-H and P-C bond activation for unsaturated diphosphine-coordinated triosmium carbonyl clusters." [Denton, Tex.] : University of North Texas, 2008. http://digital.library.unt.edu/permalink/meta-dc-6037.

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Ho, Chun-wah. "Study on osmium and manganese complexes of chiral binaphthylic tetradentate ligands and their application to asymmetric epoxidation of alkenes /." [Hong Kong : University of Hong Kong], 1994. http://sunzi.lib.hku.hk/hkuto/record.jsp?B13787020.

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Sun, Qiyu. "Human GM-CSF, IL-3 and IL-5 receptor expression and their functional domains studied with monoclonal antibodies /." Title page, contents and abstract only, 1997. http://web4.library.adelaide.edu.au/theses/09PH/09phs9569.pdf.

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陳磊碩 and Lui-sek Chan. "Chemical modification of immunoglobulins and the effects on antigen binding site affinity." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 1993. http://hub.hku.hk/bib/B29913378.

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Dissertations / Theses on the topic 'Binding sites (Biochemistry) Ligand binding (Biochemistry)'

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