4zqm
From Proteopedia
(Difference between revisions)
| (4 intermediate revisions not shown.) | |||
| Line 1: | Line 1: | ||
| + | |||
==Crystal Structure of the Catalytic Domain of the Inosine Monophosphate Dehydrogenase from Mycobacterium tuberculosis in the complex with XMP and NAD== | ==Crystal Structure of the Catalytic Domain of the Inosine Monophosphate Dehydrogenase from Mycobacterium tuberculosis in the complex with XMP and NAD== | ||
| - | <StructureSection load='4zqm' size='340' side='right' caption='[[4zqm]], [[Resolution|resolution]] 1.60Å' scene=''> | + | <StructureSection load='4zqm' size='340' side='right'caption='[[4zqm]], [[Resolution|resolution]] 1.60Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[4zqm]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ZQM OCA]. For a <b>guided tour on the structure components</b> use [ | + | <table><tr><td colspan='2'>[[4zqm]] is a 1 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=4ZQM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4ZQM FirstGlance]. <br> |
| - | </td></tr><tr id=' | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.602Å</td></tr> |
| - | <tr id=' | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene>, <scene name='pdbligand=XMP:XANTHOSINE-5-MONOPHOSPHATE'>XMP</scene></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4zqm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zqm OCA], [https://pdbe.org/4zqm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4zqm RCSB], [https://www.ebi.ac.uk/pdbsum/4zqm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4zqm ProSAT]</span></td></tr> |
</table> | </table> | ||
== Function == | == 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> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 4zqm" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Inosine monophosphate dehydrogenase 3D structures|Inosine monophosphate dehydrogenase 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| - | [[Category: | + | [[Category: Large Structures]] |
| - | [[Category: | + | [[Category: Mycobacterium tuberculosis H37Rv]] |
| - | [[Category: Gu | + | [[Category: Anderson WF]] |
| - | [[Category: Hedstrom | + | [[Category: Gu M]] |
| - | [[Category: Joachimiak | + | [[Category: Hedstrom L]] |
| - | [[Category: Kavitha | + | [[Category: Joachimiak A]] |
| - | [[Category: Kim | + | [[Category: Kavitha M]] |
| - | [[Category: Makowska-Grzyska | + | [[Category: Kim Y]] |
| - | [[Category: Maltseva | + | [[Category: Makowska-Grzyska M]] |
| - | + | [[Category: Maltseva N]] | |
| - | + | ||
| - | + | ||
| - | + | ||
Current revision
Crystal Structure of the Catalytic Domain of the Inosine Monophosphate Dehydrogenase from Mycobacterium tuberculosis in the complex with XMP and NAD
| |||||||||||
