7xp7 | pdb_00007xp7

Crystal Structure of the Flavoprotein ColB1 Catalyzing Assembly Line-Tethered Cysteine Dehydrogenation

spinqualitylabelsall models 7xp7, resolution 1.95Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7xp7 is a 4 chain structure with sequence from Streptomyces filamentosus NRRL 11379. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: FAD Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function W9FXI8_STRFL Publication Abstract from PubMed The recruitment of trans-acting enzymes by nonribosomal peptide synthetase (NRPS) assembly line is rarely reported. ColB1 is a flavin-dependent dehydrogenase that is recruited by an NRPS terminal condensation domain (Ct domain) and catalyzes peptidyl carrier protein (PCP)-tethered cysteine dehydrogenation in collismycin biosynthesis. We here report the crystal structure of ColB1 complexed with FAD and reveal a typical structural fold of acyl-CoA dehydrogenases (ACADs). However, ColB1 shows distinct structural features from ACADs in substrate recognition both at the entrance of and inside the active site. Site-directed mutagenesis and substrate modeling establish a Glu393-mediated catalytic mechanism, by which the cysteine substrate is sandwiched between Glu393 and FAD to facilitate C(alpha) proton abstraction and C(beta) hydride migration. A ColB1-PCP-Ct complex model is generated, providing structural basis for the unique recruitment interactions between ColB1 and the associated NRPS. These results add insights into the mechanisms by which trans-acting enzymes function in an assembly line. Structure-Based Mechanistic Insights into ColB1, a Flavoprotein Functioning in-trans in the 2,2'-Bipyridine Assembly Line for Cysteine Dehydrogenation.,Ma X, Tang Z, Ding W, Liu T, Yang D, Liu W, Ma M ACS Chem Biol. 2023 Jan 20;18(1):18-24. doi: 10.1021/acschembio.2c00785. Epub , 2023 Jan 5. PMID:36603145 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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