1HSZ

HUMAN BETA-1 ALCOHOL DEHYDROGENASE (ADH1B*1)

1HSZ の概要

• エントリーDOI: 10.2210/pdb1hsz/pdb
• 関連するPDBエントリー: 1DEH 1hso 1ht0
• 分子名称: CLASS I ALCOHOL DEHYDROGENASE 1, BETA SUBUNIT, ZINC ION, NICOTINAMIDE-ADENINE-DINUCLEOTIDE, ... (5 entities in total)
• 機能のキーワード: rossmann fold, alcohol dehydrogenase, zinc, oxidoreductase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm: P00325
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 81230.01

構造登録者

Niederhut, M.S.,Gibbons, B.J.,Perez-Miller, S.,Hurley, T.D. (登録日: 2000-12-27, 公開日: 2001-01-10, 最終更新日: 2023-08-09)

主引用文献

Niederhut, M.S.,Gibbons, B.J.,Perez-Miller, S.,Hurley, T.D.
Three-dimensional structures of the three human class I alcohol dehydrogenases.
Protein Sci., 10:697-706, 2001

PubMed Abstract: In contrast with other animal species, humans possess three distinct genes for class I alcohol dehydrogenase and show polymorphic variation in the ADH1B and ADH1C genes. The three class I alcohol dehydrogenase isoenzymes share approximately 93% sequence identity but differ in their substrate specificity and their developmental expression. We report here the first three-dimensional structures for the ADH1A and ADH1C*2 gene products at 2.5 and 2.0 A, respectively, and the structure of the ADH1B*1 gene product in a binary complex with cofactor at 2.2 A. Not surprisingly, the overall structure of each isoenzyme is highly similar to the others. However, the substitution of Gly for Arg at position 47 in the ADH1A isoenzyme promotes a greater extent of domain closure in the ADH1A isoenzyme, whereas substitution at position 271 may account for the lower turnover rate for the ADH1C*2 isoenzyme relative to its polymorphic variant, ADH1C*1. The substrate-binding pockets of each isoenzyme possess a unique topology that dictates each isoenzyme's distinct but overlapping substrate preferences. ADH1*B1 has the most restrictive substrate-binding site near the catalytic zinc atom, whereas both ADH1A and ADH1C*2 possess amino acid substitutions that correlate with their better efficiency for the oxidation of secondary alcohols. These structures describe the nature of their individual substrate-binding pockets and will improve our understanding of how the metabolism of beverage ethanol affects the normal metabolic processes performed by these isoenzymes.

PubMed: 11274460
DOI: 10.1110/ps.45001

実験手法

X-RAY DIFFRACTION (2.2 Å)