5zon: Difference between revisions
New page: '''Unreleased structure''' The entry 5zon is ON HOLD Authors: Description: Category: Unreleased Structures |
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The | ==Histidinol phosphate phosphatase from Mycobacterium tuberculosis== | ||
<StructureSection load='5zon' size='340' side='right'caption='[[5zon]], [[Resolution|resolution]] 1.94Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5zon]] 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=5ZON OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5ZON 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]] 1.94Å</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=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=5zon FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5zon OCA], [https://pdbe.org/5zon PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5zon RCSB], [https://www.ebi.ac.uk/pdbsum/5zon PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5zon ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/HISN_MYCTU HISN_MYCTU] Catalyzes the dephosphorylation of histidinol-phosphate to histidinol, the direct precursor of histidine. | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The absence of a histidine biosynthesis pathway in humans, coupled with histidine essentiality for survival of the important human pathogen Mycobacterium tuberculosis (Mtb), underscores the importance of the bacterial enzymes of this pathway as major anti-tuberculosis drug targets. However, the identity of the mycobacterial enzyme that functions as the histidinol phosphate phosphatase (HolPase) of this pathway remains to be established. Here, we demonstrate that the enzyme encoded by the Rv3137 gene, belonging to the inositol monophosphatase (IMPase) family, functions as the Mtb HolPase and specifically dephosphorylates histidinol phosphate. The crystal structure of Rv3137 in apo form enabled us to dissect its distinct structural features. Furthermore, the holo-complex structure revealed that a unique cocatalytic multi-zinc-assisted mode of substrate binding and catalysis is the hallmark of Mtb HolPase. Interestingly, the enzyme-substrate complex structure unveiled that although monomers possess individual catalytic sites, they share a common product-exit channel at the dimer interface. Furthermore, target-based screening against HolPase identified several small-molecule inhibitors of this enzyme. Taken together, our study unravels the missing enzyme link in the Mtb histidine biosynthesis pathway, augments our current mechanistic understanding of histidine production in Mtb, and has helped identify potential inhibitors of this bacterial pathway. | |||
Identification and structural characterization of a histidinol phosphate phosphatase from Mycobacterium tuberculosis.,Jha B, Kumar D, Sharma A, Dwivedy A, Singh R, Biswal BK J Biol Chem. 2018 May 11. pii: RA118.002299. doi: 10.1074/jbc.RA118.002299. PMID:29752410<ref>PMID:29752410</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 5zon" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Mycobacterium tuberculosis H37Rv]] | |||
[[Category: Biswal BK]] | |||
[[Category: Jha B]] | |||
[[Category: Kumar D]] | |||