5yht | pdb_00005yht

Crystal structure of a phosphatase from Mycobacterium tuberculosis in complex with its substrate

spinqualitylabelsall models 5yht, resolution 2.87Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5yht is a 2 chain structure with sequence from Myctu. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: HSA, HSO, PO4, ZN Related: 5yfl Gene: hisN, impC, Rv3137 (MYCTU) Activity: Histidinol-phosphatase, with EC number 3.1.3.15 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [HISN_MYCTU] Catalyzes the dephosphorylation of histidinol-phosphate to histidinol, the direct precursor of histidine. 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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