4zqn
From Proteopedia
(Difference between revisions)
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=4QO:2-CHLORO-N,N-DIMETHYL-5-[({2-[3-(PROP-1-EN-2-YL)PHENYL]PROPAN-2-YL}CARBAMOYL)AMINO]BENZAMIDE'>4QO</scene>, <scene name='pdbligand=IMP:INOSINIC+ACID'>IMP</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=4QO:2-CHLORO-N,N-DIMETHYL-5-[({2-[3-(PROP-1-EN-2-YL)PHENYL]PROPAN-2-YL}CARBAMOYL)AMINO]BENZAMIDE'>4QO</scene>, <scene name='pdbligand=IMP:INOSINIC+ACID'>IMP</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4zqm|4zqm]], [[4zqo|4zqo]], [[4zqp|4zqp]], [[4zqr|4zqr]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4zqm|4zqm]], [[4zqo|4zqo]], [[4zqp|4zqp]], [[4zqr|4zqr]]</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=4zqn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zqn OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4zqn RCSB], [http://www.ebi.ac.uk/pdbsum/4zqn 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=4zqn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zqn OCA], [http://pdbe.org/4zqn PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4zqn RCSB], [http://www.ebi.ac.uk/pdbsum/4zqn PDBsum]</span></td></tr> |
</table> | </table> | ||
== Function == | == Function == | ||
[[http://www.uniprot.org/uniprot/IMDH_MYCTU IMDH_MYCTU]] 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] | [[http://www.uniprot.org/uniprot/IMDH_MYCTU IMDH_MYCTU]] 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 worldwide problem and the need for new drugs is increasingly more urgent with the emergence of multidrug- and extensively-drug resistant TB. Inosine 5'-monophosphate dehydrogenase 2 (IMPDH2) from Mycobacterium tuberculosis (Mtb) is an attractive drug target. The enzyme catalyzes the conversion of inosine 5'-monophosphate into xanthosine 5'-monophosphate with the concomitant reduction of NAD+ to NADH. This reaction controls flux into the guanine nucleotide pool. We report seventeen selective IMPDH inhibitors with antitubercular activity. The crystal structures of a deletion mutant of MtbIMPDH2 in the apo form and in complex with the product XMP and substrate NAD+ are determined. We also report the structures of complexes with IMP and three structurally distinct inhibitors, including two with antitubercular activity. These structures will greatly facilitate the development of MtbIMPDH2-targeted antibiotics. | ||
| + | |||
| + | Mycobacterium tuberculosis IMPDH in Complexes with Substrates, Products and Antitubercular Compounds.,Makowska-Grzyska M, Kim Y, Gorla SK, Wei Y, Mandapati K, Zhang M, Maltseva N, Modi G, Boshoff HI, Gu M, Aldrich C, Cuny GD, Hedstrom L, Joachimiak A PLoS One. 2015 Oct 6;10(10):e0138976. doi: 10.1371/journal.pone.0138976., eCollection 2015. PMID:26440283<ref>PMID:26440283</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 4zqn" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
Revision as of 07:42, 16 December 2015
Crystal Structure of the Catalytic Domain of the Inosine Monophosphate Dehydrogenase from Mycobacterium tuberculosis in the complex with IMP and the inhibitor P41
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