5gvx
From Proteopedia
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== Function == | == Function == | ||
[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> | [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> | ||
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| - | == 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. | ||
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| - | 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> | ||
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
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| - | <div class="pdbe-citations 5gvx" style="background-color:#fffaf0;"></div> | ||
== References == | == References == | ||
<references/> | <references/> | ||
Current revision
Structural insight into dephosphorylation by Trehalose 6-phosphate Phosphatase (OtsB2) from Mycobacterium Tuberculosis
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