5gvx: Difference between revisions
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The | ==Structural insight into dephosphorylation by Trehalose 6-phosphate Phosphatase (OtsB2) from Mycobacterium Tuberculosis== | ||
<StructureSection load='5gvx' size='340' side='right' caption='[[5gvx]], [[Resolution|resolution]] 2.60Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5gvx]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5GVX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5GVX FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr> | |||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Trehalose-phosphatase Trehalose-phosphatase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.3.12 3.1.3.12] </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=5gvx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5gvx OCA], [http://pdbe.org/5gvx PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5gvx RCSB], [http://www.ebi.ac.uk/pdbsum/5gvx PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5gvx ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[[http://www.uniprot.org/uniprot/OTSB_MYCTU OTSB_MYCTU]] Removes the phosphate from trehalose 6-phosphate to produce free trehalose.<ref>PMID:15158675</ref> <ref>PMID:15703182</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Trehalose serves as a key structural component in the cell wall of Mycobacterium tuberculosis. M. tuberculosis trehalose-6-phosphate phosphatase (MtbTPP), an essential enzyme in the trehalose biosynthesis OtsAB pathway, catalyzes the dephosphorylation of trehalose-6-phosphate (trehalose-6-P) to generate trehalose, and plays a critical role in M. tuberculosis survival-associated cell wall formation and permeability. Therefore, MtbTPP (OtsB2) is considered a promising potential target for discovery of antimicrobial drugs. However, the absence of structural information of MtbTPP restrains our understanding of its underlying catalytic mechanism. Here, we report the high-resolution crystal structures of apo active MtbTPP and its trehalose-6-P bound complex. The apo structure presents a canonical haloacid dehalogenase superfamily structural fold plus an extra N-terminal domain. The catalytic center is located in a positively charged cleft between the hydrolase domain and the cap domain, demonstrating a highly conserved substrate binding pocket. The role of residues interacting with the substrate in catalysis were probed by site-directed mutagenesis. Asp147, Asp149, Asp330, and Asp331 were found to be pivotal for the enzymatic activity of MtbTPP. The MtbTPP structures reported here provide insight into a key step in the biosynthesis of trehalose, which would facilitate future development of anti-TB therapeutics.-Shan, S., Min, H., Liu, T., Jiang, D., Rao, Z. Structural insight into dephosphorylation by trehalose 6-phosphate phosphatase (OtsB2) from Mycobacterium tuberculosis. | |||
Structural insight into dephosphorylation by trehalose 6-phosphate phosphatase (OtsB2) from Mycobacterium tuberculosis.,Shan S, Min H, Liu T, Jiang D, Rao Z FASEB J. 2016 Dec;30(12):3989-3996. Epub 2016 Aug 29. PMID:27572957<ref>PMID:27572957</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 5gvx" style="background-color:#fffaf0;"></div> | |||
[[Category: | == References == | ||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Trehalose-phosphatase]] | |||
[[Category: Jiang, D]] | [[Category: Jiang, D]] | ||
[[Category: Liu, T]] | [[Category: Liu, T]] | ||
[[Category: Min, H]] | [[Category: Min, H]] | ||
[[Category: Rao, Z]] | |||
[[Category: Shan, S]] | |||
[[Category: Drug discovery]] | |||
[[Category: Hydrolase]] | |||
[[Category: Mtbtpp]] | |||
[[Category: Phosphatase]] | |||
[[Category: Trehalose]] | |||
Revision as of 09:22, 27 September 2017
Structural insight into dephosphorylation by Trehalose 6-phosphate Phosphatase (OtsB2) from Mycobacterium Tuberculosis
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