4zqr: Difference between revisions
New page: '''Unreleased structure''' The entry 4zqr is ON HOLD Authors: Kim, Y., Makowska-Grzyska, M., Gu, M., Kavitha, M., Hedstrom, L., Andesrson, W.F., Joachimiak, A., Center for Structural Ge... |
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==Crystal Structure of the Catalytic Domain of the Inosine Monophosphate Dehydrogenase from Mycobacterium tuberculosis== | |||
<StructureSection load='4zqr' size='340' side='right'caption='[[4zqr]], [[Resolution|resolution]] 1.69Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4zqr]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis_H37Rv Mycobacterium tuberculosis H37Rv]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ZQR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4ZQR FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.692Å</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=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=PGO:S-1,2-PROPANEDIOL'>PGO</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></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=4zqr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zqr OCA], [https://pdbe.org/4zqr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4zqr RCSB], [https://www.ebi.ac.uk/pdbsum/4zqr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4zqr 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®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 4zqr" style="background-color:#fffaf0;"></div> | ||
[[Category: | |||
[[Category: | ==See Also== | ||
[[Category: | *[[Inosine monophosphate dehydrogenase 3D structures|Inosine monophosphate dehydrogenase 3D structures]] | ||
[[Category: | == References == | ||
[[Category: | <references/> | ||
[[Category: | __TOC__ | ||
[[Category: | </StructureSection> | ||
[[Category: Large Structures]] | |||
[[Category: Mycobacterium tuberculosis H37Rv]] | |||
[[Category: Anderson WF]] | |||
[[Category: Gu M]] | |||
[[Category: Hedstrom L]] | |||
[[Category: Joachimiak A]] | |||
[[Category: Kavitha M]] | |||
[[Category: Kim Y]] | |||
[[Category: Makowska-Grzyska M]] | |||