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4zqp

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Revision as of 07:41, 9 March 2017

Crystal Structure of the Catalytic Domain of the Inosine Monophosphate Dehydrogenase from Mycobacterium tuberculosis in the complex with IMP and the inhibitor MAD1

Structural highlights

4zqp is a 1 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, , , , ,
Related:	4zqm, 4zqn, 4zqo
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[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]

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^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ 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. Mycobacterium tuberculosis IMPDH in Complexes with Substrates, Products and Antitubercular Compounds. PLoS One. 2015 Oct 6;10(10):e0138976. doi: 10.1371/journal.pone.0138976., eCollection 2015. PMID:26440283 doi:http://dx.doi.org/10.1371/journal.pone.0138976

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4zqp"

@@ Line 1: / Line 1: @@
 ==Crystal Structure of the Catalytic Domain of the Inosine Monophosphate Dehydrogenase from Mycobacterium tuberculosis in the complex with IMP and the inhibitor MAD1==
 <StructureSection load='4zqp' size='340' side='right' caption='[[4zqp]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
@@ Line 5: / Line 6: @@
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=IMP:INOSINIC+ACID'>IMP</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=KP3:5-O-({1-[(2E)-4-(4-HYDROXY-6-METHOXY-7-METHYL-3-OXO-1,3-DIHYDRO-2-BENZOFURAN-5-YL)-2-METHYLBUT-2-EN-1-YL]-1H-1,2,3-TRIAZOL-4-YL}METHYL)ADENOSINE'>KP3</scene>, <scene name='pdbligand=PGO:S-1,2-PROPANEDIOL'>PGO</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4zqm|4zqm]], [[4zqn|4zqn]], [[4zqo|4zqo]]</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=4zqp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zqp OCA], [http://pdbe.org/4zqp PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4zqp RCSB], [http://www.ebi.ac.uk/pdbsum/4zqp 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=4zqp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zqp OCA], [http://pdbe.org/4zqp PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4zqp RCSB], [http://www.ebi.ac.uk/pdbsum/4zqp PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4zqp ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 22: / Line 23: @@
 __TOC__
 </StructureSection>
-[[Category: Andesrson, W F]]
+[[Category: Anderson, W F]]
 [[Category: Structural genomic]]
 [[Category: Gu, M]]

4zqp

From Proteopedia

Revision as of 07:41, 9 March 2017

Crystal Structure of the Catalytic Domain of the Inosine Monophosphate Dehydrogenase from Mycobacterium tuberculosis in the complex with IMP and the inhibitor MAD1

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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