1UC4

Structure of diol dehydratase complexed with (S)-1,2-propanediol

1UC4 の概要

• エントリーDOI: 10.2210/pdb1uc4/pdb
• 関連するPDBエントリー: 1DIO 1EEX 1EGM 1EGV 1IWP 1UC5
• 分子名称: diol dehydrase alpha subunit, diol dehydrase beta subunit, diol dehydrase gamma subunit, ... (8 entities in total)
• 機能のキーワード: alpha/beta barrel, lyase
• 由来する生物種: Klebsiella oxytoca; 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 210512.29

構造登録者

Shibata, N.,Nakanishi, Y.,Fukuoka, M.,Yamanishi, M.,Yasuoka, N.,Toraya, T. (登録日: 2003-04-08, 公開日: 2003-07-22, 最終更新日: 2023-10-25)

主引用文献

Shibata, N.,Nakanishi, Y.,Fukuoka, M.,Yamanishi, M.,Yasuoka, N.,Toraya, T.
Structural rationalization for the lack of stereospecificity in coenzyme B12-dependent diol dehydratase
J.BIOL.CHEM., 278:22717-22725, 2003

PubMed Abstract: Adenosylcobalamin-dependent diol dehydratase of Klebsiella oxytoca is apparently not stereospecific and catalyzes the conversion of both (R)- and (S)-1,2-propanediol to propionaldehyde. To explain this unusual property of the enzyme, we analyzed the crystal structures of diol dehydratase in complexes with cyanocobalamin and (R)- or (S)-1,2-propanediol. (R)- and (S)-isomers are bound in a symmetrical manner, although the hydrogen-bonding interactions between the substrate and the active-site residues are the same. From the position of the adenosyl radical in the modeled "distal" conformation, it is reasonable for the radical to abstract the pro-R and pro-S hydrogens from (R)- and (S)-isomers, respectively. The hydroxyl groups in the substrate radicals would migrates from C(2) to C(1) by a suprafacial shift, resulting in the stereochemical inversion at C(1). This causes 60 degrees clockwise and 70 degrees counterclockwise rotations of the C(1)-C(2) bond of the (R)- and (S)-isomers, respectively, if viewed from K+. A modeling study of 1,1-gem-diol intermediates indicated that new radical center C(2) becomes close to the methyl group of 5'-deoxyadenosine. Thus, the hydrogen back-abstraction (recombination) from 5'-deoxyadenosine by the product radical is structurally feasible. It was also predictable that the substitution of the migrating hydroxyl group by a hydrogen atom from 5'-deoxyadenosine takes place with the inversion of the configuration at C(2) of the substrate. Stereospecific dehydration of the 1,1-gem-diol intermediates can also be rationalized by assuming that Asp-alpha335 and Glu-alpha170 function as base catalysts in the dehydration of the (R)- and (S)-isomers, respectively. The structure-based mechanism and stereochemical courses of the reaction are proposed.

PubMed: 12684496
DOI: 10.1074/jbc.M301513200

実験手法

X-RAY DIFFRACTION (1.8 Å)