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| | ==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== |
| - | <StructureSection load='5gvx' size='340' side='right' caption='[[5gvx]], [[Resolution|resolution]] 2.60Å' scene=''> | + | <StructureSection load='5gvx' size='340' side='right'caption='[[5gvx]], [[Resolution|resolution]] 2.60Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5gvx]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Myctu Myctu]. 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> | + | <table><tr><td colspan='2'>[[5gvx]] 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=5GVX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/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> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.596Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">otsB, otsB2, Rv3372 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83332 MYCTU])</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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'>[https://proteopedia.org/fgij/fg.htm?mol=5gvx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5gvx OCA], [https://pdbe.org/5gvx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5gvx RCSB], [https://www.ebi.ac.uk/pdbsum/5gvx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5gvx ProSAT]</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> | | </table> |
| | == Function == | | == 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> | + | [https://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;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Myctu]] | + | [[Category: Large Structures]] |
| - | [[Category: Trehalose-phosphatase]] | + | [[Category: Mycobacterium tuberculosis H37Rv]] |
| - | [[Category: Jiang, D]] | + | [[Category: Jiang D]] |
| - | [[Category: Liu, T]] | + | [[Category: Liu T]] |
| - | [[Category: Min, H]] | + | [[Category: Min H]] |
| - | [[Category: Rao, Z]] | + | [[Category: Rao Z]] |
| - | [[Category: Shan, S]] | + | [[Category: Shan S]] |
| - | [[Category: Drug discovery]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Mtbtpp]]
| + | |
| - | [[Category: Phosphatase]]
| + | |
| - | [[Category: Trehalose]]
| + | |
| Structural highlights
Function
OTSB_MYCTU Removes the phosphate from trehalose 6-phosphate to produce free trehalose.[1] [2]
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[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Edavana VK, Pastuszak I, Carroll JD, Thampi P, Abraham EC, Elbein AD. Cloning and expression of the trehalose-phosphate phosphatase of Mycobacterium tuberculosis: comparison to the enzyme from Mycobacterium smegmatis. Arch Biochem Biophys. 2004 Jun 15;426(2):250-7. PMID:15158675 doi:http://dx.doi.org/10.1016/j.abb.2004.02.014
- ↑ Murphy HN, Stewart GR, Mischenko VV, Apt AS, Harris R, McAlister MS, Driscoll PC, Young DB, Robertson BD. The OtsAB pathway is essential for trehalose biosynthesis in Mycobacterium tuberculosis. J Biol Chem. 2005 Apr 15;280(15):14524-9. Epub 2005 Feb 9. PMID:15703182 doi:http://dx.doi.org/10.1074/jbc.M414232200
- ↑ Shan S, Min H, Liu T, Jiang D, Rao Z. Structural insight into dephosphorylation by trehalose 6-phosphate phosphatase (OtsB2) from Mycobacterium tuberculosis. FASEB J. 2016 Dec;30(12):3989-3996. Epub 2016 Aug 29. PMID:27572957 doi:http://dx.doi.org/10.1096/fj.201600463R
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