Related ArticlesMolecular docking and NMR binding studies to identify novel inhibitors of human phosphomevalonate kinase.
Biochem Biophys Res Commun. 2013 Jan 4;430(1):313-9
Authors: Boonsri P, Neumann TS, Olson AL, Cai S, Herdendorf TJ, Miziorko HM, Hannongbua S, Sem DS
Abstract
Phosphomevalonate kinase (PMK) phosphorylates mevalonate-5-phosphate (M5P) in the mevalonate pathway, which is the sole source of isoprenoids and steroids in humans. We have identified new PMK inhibitors with virtual screening, using autodock. Promising hits were verified and their affinity measured using NMR-based (1)H-(15)N heteronuclear single quantum coherence (HSQC) chemical shift perturbation and fluorescence titrations. Chemical shift changes were monitored, plotted, and fitted to obtain dissociation constants (K(d)). Tight binding compounds with K(d)'s ranging from 6-60 ?M were identified. These compounds tended to have significant polarity and negative charge, similar to the natural substrates (M5P and ATP). HSQC cross peak changes suggest that binding induces a global conformational change, such as domain closure. Compounds identified in this study serve as chemical genetic probes of human PMK, to explore pharmacology of the mevalonate pathway, as well as starting points for further drug development.
[NMR paper] NMR- and CD-Monitored Lipid-Binding Studies Suggest a General Role for the FATC Domain as Membrane Anchor of Phosphatidyl-Inositol-3 Kinase-Related Kinases (PIKKs).
NMR- and CD-Monitored Lipid-Binding Studies Suggest a General Role for the FATC Domain as Membrane Anchor of Phosphatidyl-Inositol-3 Kinase-Related Kinases (PIKKs).
Related Articles NMR- and CD-Monitored Lipid-Binding Studies Suggest a General Role for the FATC Domain as Membrane Anchor of Phosphatidyl-Inositol-3 Kinase-Related Kinases (PIKKs).
J Biol Chem. 2013 May 13;
Authors: Sommer LA, Schaad M, Dames SA
Abstract
The FATC domain is shared by all members of the family of phosphatidylinositol-3 kinase related kinases (PIKKs). It has been...
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Application of NMR and Molecular Docking in Structure-Based Drug Discovery.
Application of NMR and Molecular Docking in Structure-Based Drug Discovery.
Application of NMR and Molecular Docking in Structure-Based Drug Discovery.
Top Curr Chem. 2011 Sep 14;
Authors: Stark JL, Powers R
Abstract
Drug discovery is a complex and costly endeavor, where few drugs that reach the clinical testing phase make it to market. High-throughput screening (HTS) is the primary method used by the pharmaceutical industry to identify initial lead compounds. Unfortunately, HTS has a high failure rate and is not particularly efficient at...
[NMR paper] Strategies for the NMR-based identification and optimization of allosteric protein kinase inhibitors.
Strategies for the NMR-based identification and optimization of allosteric protein kinase inhibitors.
Related Articles Strategies for the NMR-based identification and optimization of allosteric protein kinase inhibitors.
Chembiochem. 2005 Sep;6(9):1607-10
Authors: Jahnke W, Blommers MJ, Fernández C, Zwingelstein C, Amstutz R
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[NMR paper] The application of x-ray, NMR, and molecular modeling in the design of MMP inhibitors
The application of x-ray, NMR, and molecular modeling in the design of MMP inhibitors.
Related Articles The application of x-ray, NMR, and molecular modeling in the design of MMP inhibitors.
Curr Top Med Chem. 2004;4(12):1311-27
Authors: Rush TS, Powers R
The following review discusses the successful application of X-ray, NMR, and molecular modeling in the design of potent and selective inhibitors of matrix metalloproteinases (MMPs) and TNFalpha-converting enzyme (TACE) from Wyeth. The importance of protein and ligand mobility as it impacts...
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[NMR paper] NMR studies of internal dynamics of serine proteinase protein inhibitors: Binding reg
NMR studies of internal dynamics of serine proteinase protein inhibitors: Binding region mobilities of intact and reactive-site hydrolyzed Cucurbita maxima trypsin inhibitor (CMTI)-III of the squash family and comparison with those of counterparts of CMTI-V of the potato I family.
Related Articles NMR studies of internal dynamics of serine proteinase protein inhibitors: Binding region mobilities of intact and reactive-site hydrolyzed Cucurbita maxima trypsin inhibitor (CMTI)-III of the squash family and comparison with those of counterparts of CMTI-V of the potato I family.
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[NMR paper] NMR-based discovery of lead inhibitors that block DNA binding of the human papillomav
NMR-based discovery of lead inhibitors that block DNA binding of the human papillomavirus E2 protein.
http://www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--pubs.acs.org-images-acspubs.jpg Related Articles NMR-based discovery of lead inhibitors that block DNA binding of the human papillomavirus E2 protein.
J Med Chem. 1997 Sep 26;40(20):3144-50
Authors: Hajduk PJ, Dinges J, Miknis GF, Merlock M, Middleton T, Kempf DJ, Egan DA, Walter KA, Robins TS, Shuker SB, Holzman TF, Fesik SW
The E2 protein is required for the replication of human...
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[NMR paper] Kinetic, binding, and NMR studies of perdeuterated yeast phosphoglycerate kinase and
Kinetic, binding, and NMR studies of perdeuterated yeast phosphoglycerate kinase and its interactions with substrates.
http://www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--linkinghub.elsevier.com-ihub-images-PubMedLink.gif Related Articles Kinetic, binding, and NMR studies of perdeuterated yeast phosphoglycerate kinase and its interactions with substrates.
Arch Biochem Biophys. 1995 May 10;319(1):204-10
Authors: Shibata CG, Gregory JD, Gerhardt BS, Serpersu EH
Perdeuterated yeast phosphoglycerate kinase (2HPGK) was prepared from yeast cells...
Molecular docking and NMR binding studies to identify novel inhibitors of human phosphomevalonate kinase.
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