6J76

Structure of 3,6-anhydro-L-galactose Dehydrogenase in Complex with NAP

6J76 の概要

• エントリーDOI: 10.2210/pdb6j76/pdb
• 分子名称: Aldehyde dehydrogenase A, NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE (3 entities in total)
• 機能のキーワード: aldehyde dehydrogenase, oxidoreductase
• 由来する生物種: Vibrio variabilis
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 109019.86

構造登録者

Li, P.Y.,Wang, Y.,Chen, X.L.,Zhang, Y.Z. (登録日: 2019-01-17, 公開日: 2020-01-22, 最終更新日: 2023-11-22)

主引用文献

Wang, Y.,Li, P.Y.,Zhang, Y.,Cao, H.Y.,Wang, Y.J.,Li, C.Y.,Wang, P.,Su, H.N.,Chen, Y.,Chen, X.L.,Zhang, Y.Z.
3,6-Anhydro-L-Galactose Dehydrogenase VvAHGD is a Member of a New Aldehyde Dehydrogenase Family and Catalyzes by a Novel Mechanism with Conformational Switch of Two Catalytic Residues Cysteine 282 and Glutamate 248.
J.Mol.Biol., 432:2186-2203, 2020

PubMed Abstract: 3,6-anhydro-α-L-galactose (L-AHG) is one of the main monosaccharide constituents of red macroalgae. In the recently discovered bacterial L-AHG catabolic pathway, L-AHG is first oxidized by a NAD(P)-dependent dehydrogenase (AHGD), which is a key step of this pathway. However, the catalytic mechanism(s) of AHGDs is still unclear. Here, we identified and characterized an AHGD from marine bacterium Vibrio variabilis JCM 19239 (VvAHGD). The NADP-dependent VvAHGD could efficiently oxidize L-AHG. Phylogenetic analysis suggested that VvAHGD and its homologs represent a new aldehyde dehydrogenase (ALDH) family with different substrate preferences from reported ALDH families, named the L-AHGDH family. To explain the catalytic mechanism of VvAHGD, we solved the structures of VvAHGD in the apo form and complex with NADP and modeled its structure with L-AHG. Based on structural, mutational, and biochemical analyses, the cofactor channel and the substrate channel of VvAHGD are identified, and the key residues involved in the binding of NADP and L-AHG and the catalysis are revealed. VvAHGD performs catalysis by controlling the consecutive connection and interruption of the cofactor channel and the substrate channel via the conformational changes of its two catalytic residues Cys282 and Glu248. Comparative analyses of structures and enzyme kinetics revealed that differences in the substrate channels (in shape, size, electrostatic surface, and residue composition) lead to the different substrate preferences of VvAHGD from other ALDHs. This study on VvAHGD sheds light on the diversified catalytic mechanisms and evolution of NAD(P)-dependent ALDHs.

PubMed: 32087198
DOI: 10.1016/j.jmb.2020.02.008

実験手法

X-RAY DIFFRACTION (2.368 Å)