5z9y

Crystal structure of Mycobacterium tuberculosis thiazole synthase (ThiG) complexed with DXP

spinqualitylabelsall models 5z9y, resolution 1.48Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5z9y is a 2 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 1.48Å Ligands: DXP Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function THIG_MYCTU Catalyzes the rearrangement of 1-deoxy-D-xylulose 5-phosphate (DXP) to produce the thiazole phosphate moiety of thiamine. Sulfur is provided by the thiocarboxylate moiety of the carrier protein ThiS. In vitro, sulfur can be provided by H(2)S. Publication Abstract from PubMed Increasing drug resistance in Mycobacterium tuberculosis (Mtb) has necessitated the design of new anti-mycobacterial drugs with novel targets. Thiazole synthase (ThiG) is an essential enzyme and a potential drug target in Mtb that catalyzes the formation of the thiazole moiety of thiamin-pyrophosphate from 1-deoxy-d-xylulose-5-phosphate (DXP), dehydroglycine and ThiS-thiocarboxylate. To uncover the catalysis mechanism and design potent and selective anti-mycobacterial compounds targeting ThiG, we determined the crystal structure of MtbThiG at 1.5A resolution, for the first time, snapshotting a covalently bound substrate trapped in the catalytic pocket. The structure showed a (beta/alpha)8 barrel overall fold as well as the dimer form of MtbThiG existing in solution. In the central pocket, Lys98 is the key residue forming a protonated carbinolamine intermediate, a functional Schiff base precursor, with DXP. The carbinolamine is further stabilized by active site residues mainly through hydrogen bonds. This work revealed that a protonated carbinolamine is initially formed and then it is dehydrated to the imine form of Schiff base during the early catalysis steps. Our research will provide useful information for understanding the ThiG function and lay the basis for future drug design by targeting this essential protein. Snapshots of catalysis: Structure of covalently bound substrate trapped in Mycobacterium tuberculosis thiazole synthase (ThiG).,Zhang J, Zhang B, Zhao Y, Yang X, Huang M, Cui P, Zhang W, Li J, Zhang Y Biochem Biophys Res Commun. 2018 Feb 26;497(1):214-219. doi:, 10.1016/j.bbrc.2018.02.056. Epub 2018 Feb 8. PMID:29428731 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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