View source for 4zqp


==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=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4zqp]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Myctu Myctu]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ZQP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4ZQP FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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"><div style='overflow: auto; max-height: 3em;'>[[4zqm|4zqm]], [[4zqn|4zqn]], [[4zqo|4zqo]]</div></td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">guaB, guaB2, Rv3411c, MTCY78.17 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83332 MYCTU])</td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4zqp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zqp OCA], [https://pdbe.org/4zqp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4zqp RCSB], [https://www.ebi.ac.uk/pdbsum/4zqp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4zqp ProSAT]</span></td></tr>
</table>
== Function ==
[[https://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&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4zqp" style="background-color:#fffaf0;"></div>

==See Also==
*[[Inosine monophosphate dehydrogenase 3D structures|Inosine monophosphate dehydrogenase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Myctu]]
[[Category: Anderson, W F]]
[[Category: Structural genomic]]
[[Category: Gu, M]]
[[Category: Hedstrom, L]]
[[Category: Joachimiak, A]]
[[Category: Kavitha, M]]
[[Category: Kim, Y]]
[[Category: Makowska-Grzyska, M]]
[[Category: Center for membrane proteins of infectious disease]]
[[Category: Csgid]]
[[Category: Delta cb]]
[[Category: Impdh]]
[[Category: Mad1]]
[[Category: Oxidoreductase-oxidoreductase inhibitor complex]]