4w78

Crystal structure of the ChsH1-ChsH2 complex from Mycobacterium tuberculosis

spinqualitylabelsall models 4w78, resolution 1.54Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4w78 is a 8 chain structure with sequence from Myctd and Mycobacterium tuberculosis sumu008. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: CA, CD, CL, NA Related: 4w7b Gene: CFBR_3763 (MYCTD), TMHG_02600 (Mycobacterium tuberculosis SUMu008) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed The Mycobacterium tuberculosis (Mtb) igr operon plays an essential role in Mtb cholesterol metabolism, which is critical for pathogenesis during the latent stage of Mtb infection. Here we report the first structure of a heterotetrameric MaoC-like enoyl-CoA hydratase, ChsH1-ChsH2, which is encoded by two adjacent genes from the igr operon. We demonstrate that ChsH1-ChsH2 catalyzes the hydration of a steroid enoyl-CoA, 3-oxo-4,17-pregnadiene-20-carboxyl-CoA, in the modified beta-oxidation pathway for cholesterol side chain degradation. The ligand-bound and apoenzyme structures of ChsH1-ChsH2N reveal an unusual, modified hot-dog fold with a severely truncated central alpha-helix that creates an expanded binding site to accommodate the bulkier steroid ring system. The structures show quaternary structure shifts that accommodate the four rings of the steroid substrate and offer an explanation for why the unusual heterotetrameric assembly is utilized for hydration of this steroid. The unique alphabeta heterodimer architecture utilized by ChsH1-ChsH2 to bind its distinctive substrate highlights an opportunity for the development of new antimycobacterial drugs that target a pathway specific to Mtb. A Distinct MaoC-like Enoyl-CoA Hydratase Architecture Mediates Cholesterol Catabolism in Mycobacterium tuberculosis.,Yang M, Guja KE, Thomas ST, Garcia-Diaz M, Sampson NS ACS Chem Biol. 2014 Sep 22. PMID:25203216 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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