7cxs | pdb_00007cxs

Crystal structure of CmnK, a L-Dap formation enzyme in capreomycin biosynthesis

spinqualitylabelsall models 7cxs, resolution 1.83Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7cxs is a 2 chain structure with sequence from Saccharothrix mutabilis subsp. capreolus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.83Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function A6YEI2_STRMP Publication Abstract from PubMed Capreomycin (CMN) and viomycin (VIO) are nonribosomal peptide antituberculosis antibiotics, the structures of which contain four nonproteinogenic amino acids, including l-2,3-diaminopropionic acid (l-Dap), beta-ureidodehydroalanine, l-capreomycidine, and beta-lysine. Previous bioinformatics analysis suggested that CmnB/VioB and CmnK/VioK participate in the formation of l-Dap; however, the real substrates of these enzymes are yet to be confirmed. We herein show that starting from O-phospho-l-Ser (OPS) and l-Glu precursors, CmnB catalyzes the condensation reaction to generate a metabolite intermediate N-(1-amino-1-carboxyl-2-ethyl)glutamic acid (ACEGA), which undergoes NAD(+)-dependent oxidative hydrolysis by CmnK to generate l-Dap. Furthermore, the binding site of ACEGA and the catalytic mechanism of CmnK were elucidated with the assistance of three crystal structures, including those of apo-CmnK, the NAD(+)-CmnK complex, and CmnK in an alternative conformation. The CmnK-ACEGA docking model revealed that the glutamate alpha-hydrogen points toward the nicotinamide moiety. It provides evidence that the reaction is dependent on hydride transfer to form an imine intermediate, which is subsequently hydrolyzed by a water molecule to produce l-Dap. These findings modify the original proposed pathway and provide insights into l-Dap formation in the biosynthesis of other related natural products. Characterization of Enzymes Catalyzing the Formation of the Nonproteinogenic Amino Acid l-Dap in Capreomycin Biosynthesis.,Hsu SH, Zhang S, Huang SC, Wu TK, Xu Z, Chang CY Biochemistry. 2021 Jan 12;60(1):77-84. doi: 10.1021/acs.biochem.0c00808. Epub, 2020 Dec 23. PMID:33356147 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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