5gvx

Structural insight into dephosphorylation by Trehalose 6-phosphate Phosphatase (OtsB2) from Mycobacterium TuberculosisStructural insight into dephosphorylation by Trehalose 6-phosphate Phosphatase (OtsB2) from Mycobacterium Tuberculosis

Structural highlights 5gvx is a 1 chain structure with sequence from Mycobacterium tuberculosis H37Rv. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.596Å Ligands: Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function OTSB_MYCTU Removes the phosphate from trehalose 6-phosphate to produce free trehalose. 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

spinqualitylabelsall models 5gvx, resolution 2.60Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image