6KBL

Structure-function study of AKR4C14, an aldo-keto reductase from Thai Jasmine rice (Oryza sativa L. ssp. Indica cv. KDML105)

6KBL の概要

• エントリーDOI: 10.2210/pdb6kbl/pdb
• 分子名称: Aldo-keto reductase, CACODYLATE ION, ACETATE ION, ... (5 entities in total)
• 機能のキーワード: aldo-keto reductase (akr), aldehyde reductase, aldose reductase, rice akr, akr4c14, oxidoreductase
• 由来する生物種: Oryza sativa subsp. indica (Rice)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 35013.81

構造登録者

Songsiriritthigul, C.,Narawongsanont, R.,Guan, H.H.,Chen, C.J. (登録日: 2019-06-25, 公開日: 2020-05-06, 最終更新日: 2023-11-22)

主引用文献

Songsiriritthigul, C.,Narawongsanont, R.,Tantitadapitak, C.,Guan, H.H.,Chen, C.J.
Structure-function study of AKR4C14, an aldo-keto reductase from Thai jasmine rice (Oryza sativa L. ssp. indica cv. KDML105).
Acta Crystallogr D Struct Biol, 76:472-483, 2020

PubMed Abstract: Aldo-keto reductases (AKRs) are NADPH/NADP-dependent oxidoreductase enzymes that metabolize an aldehyde/ketone to the corresponding alcohol. AKR4C14 from rice exhibits a much higher efficiency in metabolizing malondialdehyde (MDA) than do the Arabidopsis enzymes AKR4C8 and AKR4C9, despite sharing greater than 60% amino-acid sequence identity. This study confirms the role of rice AKR4C14 in the detoxification of methylglyoxal and MDA, and demonstrates that the endogenous contents of both aldehydes in transgenic Arabidopsis ectopically expressing AKR4C14 are significantly lower than their levels in the wild type. The apo structure of indica rice AKR4C14 was also determined in the absence of the cofactor, revealing the stabilized open conformation. This is the first crystal structure in AKR subfamily 4C from rice to be observed in the apo form (without bound NADP). The refined AKR4C14 structure reveals a stabilized open conformation of loop B, suggesting the initial phase prior to cofactor binding. Based on the X-ray crystal structure, the substrate- and cofactor-binding pockets of AKR4C14 are formed by loops A, B, C and β1α1. Moreover, the residues Ser211 and Asn220 on loop B are proposed as the hinge residues that are responsible for conformational alteration while the cofactor binds. The open conformation of loop B is proposed to involve Phe216 pointing out from the cofactor-binding site and the opening of the safety belt. Structural comparison with other AKRs in subfamily 4C emphasizes the role of the substrate-channel wall, consisting of Trp24, Trp115, Tyr206, Phe216, Leu291 and Phe295, in substrate discrimination. In particular, Leu291 could contribute greatly to substrate selectivity, explaining the preference of AKR4C14 for its straight-chain aldehyde substrate.

PubMed: 32355043
DOI: 10.1107/S2059798320004313

実験手法

X-RAY DIFFRACTION (1.7 Å)