5ou3: Difference between revisions

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-'''Unreleased structure'''
-The entry 5ou3 is ON HOLD  until Paper Publication
+==M. thermoresistible IMPDH in complex with IMP and Compound 31 (AT080)==
+<StructureSection load='5ou3' size='340' side='right' caption='[[5ou3]], [[Resolution|resolution]] 1.60&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[5ou3]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5OU3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5OU3 FirstGlance]. <br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=AUN:(2~{S})-~{N}-[5-(4-bromophenyl)-1~{H}-imidazol-2-yl]-2-[4-(1-methylimidazol-4-yl)phenoxy]propanamide'>AUN</scene>, <scene name='pdbligand=IMP:INOSINIC+ACID'>IMP</scene></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=5ou3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ou3 OCA], [http://pdbe.org/5ou3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ou3 RCSB], [http://www.ebi.ac.uk/pdbsum/5ou3 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5ou3 ProSAT]</span></td></tr>
+</table>
+== Function ==
+[[http://www.uniprot.org/uniprot/G7CNL4_MYCT3 G7CNL4_MYCT3]] Catalyzes the conversion of inosine 5'-phosphate (IMP) to xanthosine 5'-phosphate (XMP), the first committed and rate-limiting step in the de novo synthesis of guanine nucleotides, and therefore plays an important role in the regulation of cell growth.[HAMAP-Rule:MF_01964]
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Tuberculosis (TB) remains a major cause of mortality worldwide, and improved treatments are needed to combat emergence of drug resistance. Inosine 5'-monophosphate dehydrogenase (IMPDH), a crucial enzyme required for de novo synthesis of guanine nucleotides, is an attractive TB drug target. Herein, we describe the identification of potent IMPDH inhibitors using fragment-based screening and structure-based design techniques. Screening of a fragment library for Mycobacterium thermoresistible ( Mth) IMPDH DeltaCBS inhibitors identified a low affinity phenylimidazole derivative. X-ray crystallography of the Mth IMPDH DeltaCBS-IMP-inhibitor complex revealed that two molecules of the fragment were bound in the NAD binding pocket of IMPDH. Linking the two molecules of the fragment afforded compounds with more than 1000-fold improvement in IMPDH affinity over the initial fragment hit.
-Authors: Ascher, D.B., Pacitto, A., Blundell, T.L.
+Fragment-Based Approach to Targeting Inosine-5'-monophosphate Dehydrogenase (IMPDH) from Mycobacterium tuberculosis.,Trapero A, Pacitto A, Singh V, Sabbah M, Coyne AG, Mizrahi V, Blundell TL, Ascher DB, Abell C J Med Chem. 2018 Mar 23. doi: 10.1021/acs.jmedchem.7b01622. PMID:29547284<ref>PMID:29547284</ref>
-Description: M. thermoresistible IMPDH in complex with IMP and Compound 31 (AT080)
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
+<div class="pdbe-citations 5ou3" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Ascher, D B]]
+[[Category: Blundell, T L]]
 [[Category: Pacitto, A]]
-[[Category: Blundell, T.L]]
+[[Category: Complex]]
-[[Category: Ascher, D.B]]
+[[Category: Fragment]]
+[[Category: Impdh]]
+[[Category: Oxidoreductase]]