7XP7

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

7XP7 の概要

• エントリーDOI: 10.2210/pdb7xp7/pdb
• 分子名称: Cyclohexanecarboxyl-CoA dehydrogenase, FLAVIN-ADENINE DINUCLEOTIDE (3 entities in total)
• 機能のキーワード: acyl-coa dehydrogenase, flavin, oxidoreductase
• 由来する生物種: Streptomyces filamentosus NRRL 11379
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 178607.03

構造登録者

Ma, X.Y.,Tang, Z.J.,Liu, W.,Ma, M. (登録日: 2022-05-03, 公開日: 2023-02-08, 最終更新日: 2023-11-29)

主引用文献

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

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: 36603145
DOI: 10.1021/acschembio.2c00785
主引用文献が同じPDBエントリー

実験手法

X-RAY DIFFRACTION (1.95 Å)