Journal articles: 'PKSim'

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Li, Ronald C., Shekman L. Wong, and Keith K. H. Chan. "EXPANDED VERSION OF PKSIM FOR PHARMACOKINETIC SIMULATIONS OF BOTH METABOLITE AND PARENT DRUGS." American Journal of Therapeutics 4, no. 1 (January 1997): 16–22. http://dx.doi.org/10.1097/00045391-199701000-00004.

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Mangzira Kemung, Hefa, Loh Teng-Hern Tan, Kok-Gan Chan, Hooi-Leng Ser, Jodi Woan-Fei Law, Learn-Han Lee, and Bey-Hing Goh. "Streptomyces sp. Strain MUSC 125 from Mangrove Soil in Malaysia with Anti-MRSA, Anti-Biofilm and Antioxidant Activities." Molecules 25, no. 15 (August 3, 2020): 3545. http://dx.doi.org/10.3390/molecules25153545.

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There is an urgent need to search for new antibiotics to counter the growing number of antibiotic-resistant bacterial strains, one of which is methicillin-resistant Staphylococcus aureus (MRSA). Herein, we report a Streptomyces sp. strain MUSC 125 from mangrove soil in Malaysia which was identified using 16S rRNA phylogenetic and phenotypic analysis. The methanolic extract of strain MUSC 125 showed anti-MRSA, anti-biofilm and antioxidant activities. Strain MUSC 125 was further screened for the presence of secondary metabolite biosynthetic genes. Our results indicated that both polyketide synthase (pks) gene clusters, pksI and pksII, were detected in strain MUSC 125 by PCR amplification. In addition, gas chromatography-mass spectroscopy (GC-MS) detected the presence of different chemicals in the methanolic extract. Based on the GC-MS analysis, eight known compounds were detected suggesting their contribution towards the anti-MRSA and anti-biofilm activities observed. Overall, the study bolsters the potential of strain MUSC 125 as a promising source of anti-MRSA and antibiofilm compounds and warrants further investigation.

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Uchiba, Mitsuhiro, Kenji Okajima, Kazunori Murakami, Hiroaki Okabe, Shosuke Okamoto, and Yoshio Okada. "Effects of Plasma Kallikrein Specific Inhibitor and Active-site Blocked Factor VIIa on the Pulmonary Vascular Injury Induced by Endotoxin in Rats." Thrombosis and Haemostasis 78, no. 04 (1997): 1209–14. http://dx.doi.org/10.1055/s-0038-1657716.

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SummaryThe acute respiratory distress syndrome (ARDS) is a serious complication of sepsis. To evaluate the role of the coagulation system in the pathogenesis of ARDS in sepsis, we examined the effects of the administration of a synthetic plasma kallikrein specific inhibitor (PKSI) and of active-site blocked factor VIIa (DEGR-VIIa) on the pulmonary vascular injury induced by E. coli endotoxin (ET) in rats. Administration of PKSI prevented the pulmonary vascular injury induced by ET as well as pulmonary histological changes in animals administered ET, but it did not affect the intravascular coagulation. The opposite effect was seen with DEGR-VIIa, which prevented the intravascular coagulation but not the pulmonary vascular injury. PKSI did not inhibit the activation of the complement system induced by ET leading to the activation of neutrophils.Findings suggest that PKSI may prevent the pulmonary vascular injury induced by ET by inhibiting kallikrein, which activates the neutrophils. The intrinsic pathway of coagulation may be more important than the extrinsic pathway in the pulmonary vascular injury produced byET.

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Ginolhac, Aurélien, Cyrille Jarrin, Benjamin Gillet, Patrick Robe, Petar Pujic, Karine Tuphile, Hélène Bertrand, et al. "Phylogenetic Analysis of Polyketide Synthase I Domains from Soil Metagenomic Libraries Allows Selection of Promising Clones." Applied and Environmental Microbiology 70, no. 9 (September 2004): 5522–27. http://dx.doi.org/10.1128/aem.70.9.5522-5527.2004.

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ABSTRACT The metagenomic approach provides direct access to diverse unexplored genomes, especially from uncultivated bacteria in a given environment. This diversity can conceal many new biosynthetic pathways. Type I polyketide synthases (PKSI) are modular enzymes involved in the biosynthesis of many natural products of industrial interest. Among the PKSI domains, the ketosynthase domain (KS) was used to screen a large soil metagenomic library containing more than 100,000 clones to detect those containing PKS genes. Over 60,000 clones were screened, and 139 clones containing KS domains were detected. A 700-bp fragment of the KS domain was sequenced for 40 of 139 randomly chosen clones. None of the 40 protein sequences were identical to those found in public databases, and nucleic sequences were not redundant. Phylogenetic analyses were performed on the protein sequences of three metagenomic clones to select the clones which one can predict to produce new compounds. Two PKS-positive clones do not belong to any of the 23 published PKSI included in the analysis, encouraging further analyses on these two clones identified by the selection process.

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Świgoń, Marzena, and Karsten Weber. "Managing Knowledge and Information by Students." Journal of Information & Knowledge Management 13, no. 04 (December 2014): 1450030. http://dx.doi.org/10.1142/s0219649214500300.

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The concept of Personal Knowledge and Information Management (PKIM) is based, among others, on two theories: Personal Information Management (PTM) and Personal Knowledge Management (PKM), which hitherto were both subjects of separate studies. Moreover, the concept of PKIM is related to IL, which is a concept of information skills and competences of individuals — a person who manages knowledge has to be information literate. Some of the empirical studies results in the field of PKIM, started in Poland and recently continued in Germany, are presented. As the research method an unstructured questionnaire with open questions was used. Given the results of the survey as well as taking into account the subject literature, the concepts of PIM, PKM, and Information Literacy (IL) seem to be compatible and connected with each other. Our respondents perceive Knowledge and Information as well as knowledge management (KM) and information management (IM) in the context of learning and studying as integrated areas of interests. Although they do see differences between them, interconnections and relations seem more important. Furthermore, KM and IM are recognized as tools of coping with information overload. All aspects that have repercussions on KM and IM are related to three categories: personal characteristics, environment (macro and micro environment), and knowledge and information sources.

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Mien, Pham Thi, Dao Viet Ha, Hoang Xuan Ben, Bin Chen, Lan Liu, and Phan Minh-Thu. "Antimicrobial Activities of Sponge-Derived Microorganisms from Coastal Waters of Central Vietnam." Journal of Marine Science and Engineering 8, no. 8 (August 8, 2020): 594. http://dx.doi.org/10.3390/jmse8080594.

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Bacteria associated with invertebrates are considered as good sources for biologically active compounds. Sponge-derived bacteria were screened for antimicrobial activities, the presence of the cluster genes of polyketide synthases (PKSs) and non-ribosomal peptide synthetases (NRPSs), and through a colony picking method. Crude extracts of broth cultures were tested for microbial inhibition. Eleven out of 25 isolated strains showed inhibition of at least one of eight tested indicator microorganisms. Antimicrobial activities were observed in the strains coded HM5, HM6, and HM9 with the presence of NRPS and PKSII genes, whereas the isolate HM21 held both NRPS and PKSII and inhibited only the growth of Bacillus subtilis by the well diffusion method and only inhibited Serratia marcescens by the colony picking method. Two isolates, HM5 and HM6, belonged to the species of Bacillus. Interestingly, the isolate HM9 was nearest to Streptomyces mexicanusT NBRC100915 (GenBank accession number AB249966) with 94% sequence similarity. This potent strain HM9 could possibly be considered as a new species and a good source for bioactive compound discovery. Some isolates showed NRPS/PKS genes but did not exhibit antimicrobial activity. Thus, we suggested that both molecular and traditional methods should be conducted for the screening of antimicrobial producers.

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Oiwa, Kazuhiro, Osamu Matsuo, Shigeru Ueshima, Kiyotaka Okada, Yoshio Okada, Shosuke Okamoto, John Giddings, Junichiro Yamamoto, and Masaru Hashimoto. "Suppression of argatroban-induced endogenous thrombolysis by PKSI-527, and antibodies to TPA and UPA, evaluated in a rat arterial thrombolysis model." Thrombosis and Haemostasis 89, no. 05 (2003): 820–25. http://dx.doi.org/10.1055/s-0037-1613467.

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SummaryWe have previously confirmed, using a rat mesenteric arteriole thrombolysis model, that thrombin inhibition induces endogenous thrombolysis in vivo. In addition, we have shown that thrombin-activatable fibrinolysis inhibitor (TAFI) plays a role in the down regulation of endogenous thrombolysis. However, the mechanism of endogenous thrombolysis or spontaneous plasmin generation in vivo remains unclear.It has been shown in an in vitro system that plasma kallikrein activates pro-urokinase (pro uPA) and/or plasminogen, resulting in plasmin generation. These findings suggest that spontaneous fibrinolysis might be mediated by tPA and plasma kallikrein-dependent uPA. The aim of the present study was to examine whether these mechanisms play a dominant role in endogenous thrombolysis in vivo, using our rat mesenteric arterial thrombolysis model.Argatroban infusion enhanced endogenous thrombolysis. PKSI-527, anti uPA and anti tPA IgGs suppressed argatroban-induced thrombolysis. Also, the antibody IgG preparations suppressed endogenous thrombolysis in the absence of argatroban. In the presence of PKSI-527, anti tPA IgG was more effective than anti uPA IgG in suppressing argatroban-induced thrombolysis. The results suggested that both tPA and plasma kallikrein-mediated uPA activation and tPA release contribute to endogenous fibrinolytic or thrombolytic mechanisms.

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Ramadoan, Sri, Pudji Muljono, and Ismail Pulungan. "PERAN PKSM DALAM MENINGKATKAN FUNGSI KELOMPOK TANI DAN PARTISIPASI MASYARAKAT DI KABUPATEN BIMA, NTB." Jurnal Penelitian Sosial dan Ekonomi Kehutanan 10, no. 3 (September 30, 2013): 199–210. http://dx.doi.org/10.20886/jpsek.2013.10.3.199-210.

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Ramadoan, Sri, Pudji Muljono, and Ismail Pulungan. "PERAN PKSM DALAM MENINGKATKAN FUNGSI KELOMPOK TANI DAN PARTISIPASI MASYARAKAT DI KABUPATEN BIMA, NTB." Jurnal Penelitian Sosial dan Ekonomi Kehutanan 10, no. 3 (September 2013): 199–210. http://dx.doi.org/10.20886/jsek.2013.10.3.199-210.

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10

Chikita, Wulan. "ANALISIS KUALITAS BUTIR SOAL UJIAN AKHIR SEMESTER GASAL MATA PELAJARAN PKSM KELAS XI TEKNIK SEPEDA MOTOR." Jurnal Pendidikan Vokasi Otomotif 2, no. 1 (July 20, 2020): 23–32. http://dx.doi.org/10.21831/jpvo.v2i1.28361.

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This research was conducted with the aim to determine the quality of items about odd Semester Final Exam Subjects of Electrical Maintenance of Class XI Motorcycle Engineering at SMK Negeri 1 Bumiratu Nuban Academic Year 2018/2019. The research method used is descriptive method with a quantitative approach. The data collection technique uses the documentation method, to obtain test questions and answer keys as well as answers to all students who take the exam. The population of the study was grade XI Motorcycle Engineering SMK Negeri 1 Bumiratu Nuban 2018/2019. The results in terms of the question validity aspects as much as 57% including valid categories and 43% invalid. In terms of reliability, the reliability coefficient is 0.79 which means it has a high coefficient. Then in terms of the level of difficulty as much as 5% including the easy category, 53% including the medium category, 37% including the difficult category and 5% including the very difficult category. In terms of distinguishing factors, there were 5% of questions including excellent categories, 43% including good categories, 20% including sufficient categories, 22% including bad categories and 10% including categories that had to be discarded. From the aspect of deceptive effectiveness, there are only 7.5% of questions for which all the deceivers function effectively.

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11

Amir, Ahmad Nabil. "Dr Siddiq Fadzil dan Derap Perjuangannya." Borneo International Journal of Islamic Studies 2, no. 1 (December 30, 2019): 101–11. http://dx.doi.org/10.21093/bijis.v2i1.1631.

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Kertas ini menelaah buku Melayu dan Islam: Martabat Umat dan Daulat Rakyat karya Dr Siddiq Fadzil. Setelah diluncurkan pada 25 Jun 2012 di Hotel De Palma, Ampang, buku Melayu dan Islam: Martabat Umat dan Daulat Rakyat karya Dr Siddiq Fadzil terus diangkat dan “siap ditanggapi” oleh khalayak pembaca dan intelek. Dr Siddiq lahir di kalangan pemikir dan kelompok pembaharu di tanah air; dan merupakan aktivis dan pemimpin Islam yang besar yang menonjol dalam kegiatan intelek dan budaya yang luas. Beliau merupakan penggerak penting gerakan PKPIM (Persatuan Kebangsaan Pelajar Islam Malaysia), ABIM (Angkatan Belia Islam Malaysia) dan WADAH (Wadah Pencerdasan Umat Malaysia) dan telah bergelut dalam perjuangan bangsa sejak empat dekad yang lampau. Artikel ini cuba merumuskan sumbangannya dalam buku Melayu dan Islam ini sebagai suatu koreksi budaya dalam mengangkat diskusi tentang tradisi dan ciri budaya yang signifikan di kepulauan Melayu-Indonesia yang berakar dengan nilai rasionalisme dan humanisme Islam yang kental dan faham-faham pemikiran yang ideal yang telah mengangkat dan mempertahankan nilai kebudayaan dan peradabannya sejak masuknya Islam ke nusantara.

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12

El-Haroun, H., D. L. Clarke, K. Deacon, D. Bradbury, A. Clayton, A. Sutcliffe, and Alan J. Knox. "IL-1β, BK, and TGF-β1 attenuate PGI2-mediated cAMP formation in human pulmonary artery smooth muscle cells by multiple mechanisms involving p38 MAP kinase and PKA." American Journal of Physiology-Lung Cellular and Molecular Physiology 294, no. 3 (March 2008): L553—L562. http://dx.doi.org/10.1152/ajplung.00044.2006.

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We have previously shown that interleukin (IL)-1β, transforming growth factor (TGF)-β1, or bradykinin (BK) impair cAMP generation in response to prostacyclin analogs in human pulmonary artery smooth muscle (PASM), suggesting that inflammation can impair the effects of prostacyclin analogs on PASM in pulmonary hypertension. Here we explored the biochemical mechanisms involved. We found that IL-1β, BK, and TGF-β1 reduced adenylyl cyclase isoform 1, 2, and 4 mRNA, increased Gαi protein levels, and reduced prostacyclin receptor (IP receptor) mRNA expression. In contrast, Gαs protein levels were unchanged. Protein kinase A (PKA) (H-89, KT-2750, PKIm) and p38 mitogen-activated protein (MAP) kinase (SB-202190) inhibitors attenuated these effects, but protein kinase C (bisindolylmaleide) or phosphoinositol 3-kinase (LY-294002) inhibitors did not. Fluorescent kemptide assay and Western blotting confirmed that PKA and p38 MAP kinase were activated by IL-1β, BK, and TGF-β1. These studies suggest that IL-1β, BK, and TGF-β1 impair IP receptor-mediated cAMP accumulation by multiple effects on different components of the signaling pathway and that these effects are PKA and p38 MAP kinase dependent.

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Adams, Gregory N., Gretchen A. LaRusch, Evi Stavrou, Yihua Zhou, Marvin T. Nieman, Gretta H. Jacobs, Yingjie Cui, et al. "Murine prolylcarboxypeptidase depletion induces vascular dysfunction with hypertension and faster arterial thrombosis." Blood 117, no. 14 (April 7, 2011): 3929–37. http://dx.doi.org/10.1182/blood-2010-11-318527.

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Abstract Prolylcarboxypeptidase (PRCP) activates prekallikrein to plasma kallikrein, leading to bradykinin liberation, and degrades angiotensin II. We now identify PRCP as a regulator of blood vessel homeostasis. β-Galactosidase staining in PRCPgt/gt mice reveals expression in kidney and vasculature. Invasive telemetric monitorings show that PRCPgt/gt mice have significantly elevated blood pressure. PRCPgt/gt mice demonstrate shorter carotid artery occlusion times in 2 models, and their plasmas have increased thrombin generation times. Pharmacologic inhibition of PRCP with Z-Pro-Prolinal or plasma kallikrein with soybean trypsin inhibitor, Pro-Phe-Arg-chloromethylketone or PKSI 527 also shortens carotid artery occlusion times. Aortic and renal tissues have uncoupled eNOS and increased reactive oxygen species (ROS) in PRCPgt/gt mice as detected by dihydroethidium or Amplex Red fluorescence or lucigenin luminescence. The importance of ROS is evidenced by the fact that treatment of PRCPgt/gt mice with antioxidants (mitoTEMPO, apocynin, Tempol) abrogates the hypertensive, prothrombotic phenotype. Mechanistically, our studies reveal that PRCPgt/gt aortas express reduced levels of Kruppel-like factors 2 and 4, thrombomodulin, and eNOS mRNA, suggesting endothelial cell dysfunction. Further, PRCP siRNA treatment of endothelial cells shows increased ROS and uncoupled eNOS and decreased protein C activation because of thrombomodulin inactivation. Collectively, our studies identify PRCP as a novel regulator of vascular ROS and homeostasis.

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FUKUMIZU, Atsuko, Yoko TSUDA, Keiko WANAKA, Mayako TADA, Shosuke OKAMOTO, Akiko HIJIKATA-OKUNOMIYA, and Yoshio OKADA. "Amino Acids and Peptides. LIII. Synthesis and Biological Activities of Some Pseudo-Peptide Analogs of PKSI-527, a Plasma Kallikrein Selective Inhibitor. The Importance of the Peptide Backbone." CHEMICAL & PHARMACEUTICAL BULLETIN 47, no. 8 (1999): 1141–44. http://dx.doi.org/10.1248/cpb.47.1141.

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15

Tomoo, K., K. Satoh, Y. Tsuda, K. Wanaka, S. Okamoto, A. Hijikata-Okunomiya, Y. Okada, and T. Ishida. "Binding Diversity of a Noncovalent-Type Low-Molecular-Weight Serine Protease Inhibitor and Function of a Catalytic Water Molecule: X-Ray Crystal Structure of PKSI-527-Inhibited Trypsin." Journal of Biochemistry 129, no. 3 (March 1, 2001): 455–60. http://dx.doi.org/10.1093/oxfordjournals.jbchem.a002877.

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Wang, Liuqing, Nan Jiang, Duo Wang, and Meng Wang. "Effects of Essential Oil Citral on the Growth, Mycotoxin Biosynthesis and Transcriptomic Profile of Alternaria alternata." Toxins 11, no. 10 (September 20, 2019): 553. http://dx.doi.org/10.3390/toxins11100553.

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Alternaria alternata is a critical phytopathogen that causes foodborne spoilage and produces a polyketide mycotoxin, alternariol (AOH), and its derivative, alternariol monomethyl ether (AME). In this study, the inhibitory effects of the essential oil citral on the fungal growth and mycotoxin production of A. alternata were evaluated. Our findings indicated that 0.25 μL/mL (222.5 μg/mL) of citral completely suppressed mycelial growth as the minimum inhibitory concentration (MIC). Moreover, the 1/2MIC of citral could inhibit more than 97% of the mycotoxin amount. Transcriptomic profiling was performed by comparative RNA-Seq analysis of A. alternata with or without citral treatment. Out of a total of 1334 differentially expressed genes (DEGs), 621 up-regulated and 713 down-regulated genes were identified under citral stress conditions. Numerous DEGs for cell survival, involved in ribosome and nucleolus biogenesis, RNA processing and metabolic processes, and protein processing, were highly expressed in response to citral. However, a number of DEGs responsible for the metabolism of several carbohydrates and amino acids, sulfate and glutathione metabolism, the metabolism of xenobiotics and transporter activity were significantly more likely to be down-regulated. Citral induced the disturbance of cell integrity through the disorder of gene expression, which was further confirmed by the fact that exposure to citral caused irreversibly deleterious disruption of fungal spores and the inhibition of ergosterol biosynthesis. Citral perturbed the balance of oxidative stress, which was likewise verified by a reduction of total antioxidative capacity. In addition, citral was able to modulate the down-regulation of mycotoxin biosynthetic genes, including pksI and omtI. The results provide new insights for exploring inhibitory mechanisms and indicate citral as a potential antifungal and antimytoxigenic alternative for cereal storage.

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17

Gauthier-Rouvière, C., M. Vandromme, N. Lautredou, Q. Q. Cai, F. Girard, A. Fernandez, and N. Lamb. "The serum response factor nuclear localization signal: general implications for cyclic AMP-dependent protein kinase activity in control of nuclear translocation." Molecular and Cellular Biology 15, no. 1 (January 1995): 433–44. http://dx.doi.org/10.1128/mcb.15.1.433.

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We have identified a basic sequence in the N-terminal region of the 67-kDa serum response factor (p67SRF or SRF) responsible for its nuclear localization. A peptide containing this nuclear localization signal (NLS) translocates rabbit immunoglobulin G (IgG) into the nucleus as efficiently as a peptide encoding the simian virus 40 NLS. This effect is abolished by substituting any two of the four basic residues in this NLS. Overexpression of a modified form of SRF in which these basic residues have been mutated confirms the absolute requirement for this sequence, and not the other basic amino acid sequences adjacent to it, in the nuclear localization of SRF. Since this NLS is in close proximity to potential phosphorylation sites for the cAMP-dependent protein kinase (A-kinase), we further investigated if A-kinase plays a role in the nuclear location of SRF. The nuclear transport of SRF proteins requires basal A-kinase activity, since inhibition of A-kinase by using either the specific inhibitory peptide PKIm or type II regulatory subunits (RII) completely prevents the nuclear localization of plasmid-expressed tagged SRF or an SRF-NLS-IgG conjugate. Direct phosphorylation of SRF by A-kinase can be discounted in this effect, since mutation of the putative phosphorylation sites in either the NLS peptide or the encoded full-length SRF protein had no effect on nuclear transport of the mutants. Finally, in support of an implication of A-kinase-dependent phosphorylation in a more general mechanism affecting nuclear import, we show that the nuclear transport of a simian virus 40-NLS-conjugated IgG or purified cyclin A protein is also blocked by inhibition of A-kinase, even though neither contains any potential sites for phosphorylation by A-kinase or can be phosphorylated by A-kinase in vitro.

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18

Adams, Gregory, Gretchen LaRusch, Evi Stavrou, Yihua Zhou, Marvin T. Nieman, Gretta Jacobs, Yingjie Cui, et al. "Prolylcarboxypeptidase Deficiency Is a Risk Factor for Arterial Thrombosis and Hypertension." Blood 116, no. 21 (November 19, 2010): 651. http://dx.doi.org/10.1182/blood.v116.21.651.651.

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Abstract Abstract 651 Background. Prolylcarboxypeptidase (PRCP), an S28 serine protease, degrades bradykinin, angiotensin II, and alpha melanocyte stimulating hormone and activates prekallikrein to plasma kallikrein (Blood 103:4554, 2004). In GWAS, it has been recognized as a risk factor for metabolic syndrome, hypertension, and pre-eclampsia. We postulated that PRCP murine hypomorphs (PRCPgt/gt) have a cardiovascular phenotype. Methods and Results. PRCP is mostly found in kidney in proximal tubules. In arteries, it is found both on endothelium and in media. A gene-trap murine hypomorph was created with 7% mRNA and 23% PRCP antigen in renal tissue. Using the Rose Bengal carotid artery thrombosis models, PRCPgt/gt mice had shorter carotid artery occlusion times (24±3 min [mean±SD]) compared to wild type (52±8 min). On a 4% ferric chloride carotid artery thrombosis assay PRCPgt/gt occluded in 21±8 min whereas wild type do not occlude at 60 min. Pharmacologic inhibition of PRCP with Z-pro-prolinal or plasma kallikrein with soybean trypsin inhibitor, Pro-Phe-Arg-Chloromethylketone or PKSI-572 in 3 mouse strains also shortened the time to carotid artery occlusion. PRCPgt/gt were constitutively hypertensive during the late night cycle (122±5 mm Hg mean arterial pressure vs 114±6 mm Hg for wildtype) as measured by carotid artery telemetry. Treatment of these animals with the mitochondria specific antioxidant mitoTEMPO significantly reduced (113±7 mm Hg) the elevated BP. Plasma angiotensin II and bradykinin levels were unaltered in PRCPgt/gt. PRCPgt/gt plasma had a significant increase in contact activation-induced thrombin generation. Aortic and renal reactive oxygen species (ROS) were increased (3.2-fold and 2.8-fold, respectively) in PRCPgt/gt mice as determined by dihydroethidium (DHE) fluorescence. PRCPgt/gt aortic and renal superoxide measured by lucigenin luminescence also was increased (1.6-fold and 1.7-fold, respectively). In PRCPgt/gt kidneys Amplex Red fluorescence, a measure of hydrogen peroxide, was increased 2.4-fold. Renal tissue had 1.6-fold increased uncoupled eNOS on SDS-PAGE. Arterial occlusion times in PRCPgt/gt were corrected by treatment with antioxidant apocynin or tempol. PRCP siRNA knockdowns in HUVEC or mesenchymal embryonic fibroblasts prepared from PRCPgt/gt embryos had increased constitutive DHE fluorescent ROS (2.1-fold and 1.4-fold, respectively). PRCPgt/gt aorta had decreased expression of Kruppel-like factors 2 and 4, thrombomodulin and eNOS. Moreover, PRCP knockdowns in HUVEC had 36% reduced eNOS mRNA expression. Conclusion. These investigations indicate that PRCP is a specific gene/protein target for arterial thrombosis risk and hypertension. Its presence modulates constitutive cell and tissue ROS. Arterial thrombosis risk is related to effect of ROS on endothelial cell anticoagulant mechanisms. Disclosures: No relevant conflicts of interest to declare.

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19

Zaliani, A., C. Mueller, and M. Rarey. "Prediction of kinase inhibitors cross-reaction on the basis of kinase ATP cavity similarities: a study using PKSIM protein similarity score." Chemistry Central Journal 2, S1 (March 2008). http://dx.doi.org/10.1186/1752-153x-2-s1-p19.

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20

Nair, Asha V., Alice Robson, Thomas D. Ackrill, Marisa Till, Matthew J. Byrne, Catherine R. Back, Kavita Tiwari, Jonathan A. Davies, Christine L. Willis, and Paul R. Race. "Structure and mechanism of a dehydratase/decarboxylase enzyme couple involved in polyketide β-methyl branch incorporation." Scientific Reports 10, no. 1 (September 18, 2020). http://dx.doi.org/10.1038/s41598-020-71850-w.

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Abstract Complex polyketides of bacterial origin are biosynthesised by giant assembly-line like megaenzymes of the type 1 modular polyketide synthase (PKS) class. The trans-AT family of modular PKSs, whose biosynthetic frameworks diverge significantly from those of the archetypal cis-AT type systems represent a new paradigm in natural product enzymology. One of the most distinctive enzymatic features common to trans-AT PKSs is their ability to introduce methyl groups at positions β to the thiol ester in the growing polyketide chain. This activity is achieved through the action of a five protein HCS cassette, comprising a ketosynthase, a 3-hydroxy-3-methylglutaryl-CoA synthase, a dehydratase, a decarboxylase and a dedicated acyl carrier protein. Here we report a molecular level description, achieved using a combination of X-ray crystallography, in vitro enzyme assays and site-directed mutagenesis, of the bacillaene synthase dehydratase/decarboxylase enzyme couple PksH/PksI, responsible for the final two steps in β-methyl branch installation in this trans-AT PKS. Our work provides detailed mechanistic insight into this biosynthetic peculiarity and establishes a molecular framework for HCS cassette enzyme exploitation and manipulation, which has future potential value in guiding efforts in the targeted synthesis of functionally optimised ‘non-natural’ natural products.

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Journal articles on the topic 'PKSim'

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