5MST

Structure of the A domain of carboxylic acid reductase (CAR) from Segniliparus rugosus in complex with AMP and a co-purified carboxylic acid

5MST の概要

• エントリーDOI: 10.2210/pdb5mst/pdb
• 分子名称: Thioester reductase domain-containing protein, CALCIUM ION, FUMARIC ACID, ... (5 entities in total)
• 機能のキーワード: adenylation domain, carboxylic acid reductase, oxidoreductase
• 由来する生物種: Segniliparus rugosus ATCC BAA-974
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 257823.23

構造登録者

Gahloth, D.,Leys, D. (登録日: 2017-01-05, 公開日: 2017-07-05, 最終更新日: 2024-01-17)

主引用文献

Gahloth, D.,Dunstan, M.S.,Quaglia, D.,Klumbys, E.,Lockhart-Cairns, M.P.,Hill, A.M.,Derrington, S.R.,Scrutton, N.S.,Turner, N.J.,Leys, D.
Structures of carboxylic acid reductase reveal domain dynamics underlying catalysis.
Nat. Chem. Biol., 13:975-981, 2017

PubMed Abstract: Carboxylic acid reductase (CAR) catalyzes the ATP- and NADPH-dependent reduction of carboxylic acids to the corresponding aldehydes. The enzyme is related to the nonribosomal peptide synthetases, consisting of an adenylation domain fused via a peptidyl carrier protein (PCP) to a reductase termination domain. Crystal structures of the CAR adenylation-PCP didomain demonstrate that large-scale domain motions occur between the adenylation and thiolation states. Crystal structures of the PCP-reductase didomain reveal that phosphopantetheine binding alters the orientation of a key Asp, resulting in a productive orientation of the bound nicotinamide. This ensures that further reduction of the aldehyde product does not occur. Combining crystallography with small-angle X-ray scattering (SAXS), we propose that molecular interactions between initiation and termination domains are limited to competing PCP docking sites. This theory is supported by the fact that (R)-pantetheine can support CAR activity for mixtures of the isolated domains. Our model suggests directions for further development of CAR as a biocatalyst.

PubMed: 28719588
DOI: 10.1038/nchembio.2434

実験手法

X-RAY DIFFRACTION (1.72 Å)