7XP7
Crystal Structure of the Flavoprotein ColB1 Catalyzing Assembly Line-Tethered Cysteine Dehydrogenation
Summary for 7XP7
| Entry DOI | 10.2210/pdb7xp7/pdb |
| Descriptor | Cyclohexanecarboxyl-CoA dehydrogenase, FLAVIN-ADENINE DINUCLEOTIDE (3 entities in total) |
| Functional Keywords | acyl-coa dehydrogenase, flavin, oxidoreductase |
| Biological source | Streptomyces filamentosus NRRL 11379 |
| Total number of polymer chains | 4 |
| Total formula weight | 178607.03 |
| Authors | Ma, X.Y.,Tang, Z.J.,Liu, W.,Ma, M. (deposition date: 2022-05-03, release date: 2023-02-08, Last modification date: 2023-11-29) |
| Primary citation | Ma, X.,Tang, Z.,Ding, W.,Liu, T.,Yang, D.,Liu, W.,Ma, M. Structure-Based Mechanistic Insights into ColB1, a Flavoprotein Functioning in-trans in the 2,2'-Bipyridine Assembly Line for Cysteine Dehydrogenation. Acs Chem.Biol., 18:18-24, 2023 Cited by PubMed Abstract: The recruitment of -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 proton abstraction and C 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 -acting enzymes function in an assembly line. PubMed: 36603145DOI: 10.1021/acschembio.2c00785 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.95 Å) |
Structure validation
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