5etq: Difference between revisions
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<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CSO:S-HYDROXYCYSTEINE'>CSO</scene></td></tr> | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CSO:S-HYDROXYCYSTEINE'>CSO</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4m5h|4m5h]], [[5etk|5etk]], [[5etl|5etl]], [[5etm|5etm]], [[5etn|5etn]], [[5eto|5eto]], [[5etp|5etp]], [[5etr|5etr]], [[5ets|5ets]], [[5ett|5ett]], [[5etv|5etv]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4m5h|4m5h]], [[5etk|5etk]], [[5etl|5etl]], [[5etm|5etm]], [[5etn|5etn]], [[5eto|5eto]], [[5etp|5etp]], [[5etr|5etr]], [[5ets|5ets]], [[5ett|5ett]], [[5etv|5etv]]</td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5etq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5etq OCA], [http://pdbe.org/5etq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5etq RCSB], [http://www.ebi.ac.uk/pdbsum/5etq PDBsum]</span></td></tr> | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5etq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5etq OCA], [http://pdbe.org/5etq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5etq RCSB], [http://www.ebi.ac.uk/pdbsum/5etq PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5etq ProSAT]</span></td></tr> | ||
</table> | </table> | ||
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Revision as of 05:35, 13 July 2016
S. aureus 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase complexed with AMPCPP and inhibitor at 1.96 angstrom resolutionS. aureus 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase complexed with AMPCPP and inhibitor at 1.96 angstrom resolution
Structural highlights
Publication Abstract from PubMed6-Hydroxymethyl-7,8-dihydropterin pyrophosphokinase (HPPK) is a member of the folate biosynthesis pathway found in prokaryotes and lower eukaryotes that catalyzes the pyrophosphoryl transfer from the ATP cofactor to a 6-hydroxymethyl-7,8-dihydropterin substrate. We report the chemical synthesis of a series of S-functionalized 8-mercaptoguanine (8MG) analogues as substrate site inhibitors of HPPK and quantify binding against the E. coli and S. aureus enzymes (EcHPPK and SaHPPK). The results demonstrate that analogues incorporating acetophenone-based substituents have comparable affinities for both enzymes. Preferential binding of benzyl-substituted 8MG derivatives to SaHPPK was reconciled when a cryptic pocket unique to SaHPPK was revealed by X-ray crystallography. Differential chemical shift perturbation analysis confirmed this to be a common mode of binding for this series to SaHPPK. One compound (41) displayed binding affinities of 120 nM and 1.76 muM for SaHPPK and EcHPPK, respectively, and represents a lead for the development of more potent and selective inhibitors of SaHPPK. Structural Basis for the Selective Binding of Inhibitors to 6-Hydroxymethyl-7,8-dihydropterin Pyrophosphokinase from Staphylococcus aureus and Escherichia coli.,Dennis ML, Pitcher NP, Lee MD, DeBono AJ, Wang ZC, Harjani JR, Rahmani R, Cleary B, Peat TS, Baell JB, Swarbrick JD J Med Chem. 2016 Apr 26. PMID:27094768[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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