5AG3

Chorismatase mechanisms reveal fundamentally different types of reaction in a single conserved protein fold

5AG3 の概要

• エントリーDOI: 10.2210/pdb5ag3/pdb
• 分子名称: PUTATIVE PTERIDINE-DEPENDENT DIOXYGENASE, 3-(2-CARBOXYETHYL)BENZOIC ACID, SULFATE ION, ... (5 entities in total)
• 機能のキーワード: oxidoreductase, protein
• 由来する生物種: STREPTOMYCES HYGROSCOPICUS
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 114658.37

構造登録者

Hubrich, F.,Juneja, P.,Mueller, M.,Diederichs, K.,Welte, W.,Andexer, J.N. (登録日: 2015-01-28, 公開日: 2015-08-19, 最終更新日: 2024-01-10)

主引用文献

Hubrich, F.,Juneja, P.,Mueller, M.,Diederichs, K.,Welte, W.,Andexer, J.N.
Chorismatase Mechanisms Reveal Fundamentally Different Types of Reaction in a Single Conserved Protein Fold.
J.Am.Chem.Soc., 137:11032-, 2015

PubMed Abstract: Chorismatases are a class of chorismate-converting enzymes involved in the biosynthetic pathways of different natural products, many of them with interesting pharmaceutical characteristics. So far, three subfamilies of chorismatases are described that convert chorismate into different (dihydro-)benzoate derivatives (CH-FkbO, CH-Hyg5, and CH-XanB2). Until now, the detailed enzyme mechanism and the molecular basis for the different reaction products were unknown. Here we show that the CH-FkbO and CH-Hyg5 subfamilies share the same protein fold, but employ fundamentally different reaction mechanisms. While the FkbO reaction is a typical hydrolysis, the Hyg5 reaction proceeds intramolecularly, most likely via an arene oxide intermediate. Two nonconserved active site residues were identified that are responsible for the different reaction mechanisms in CH-FkbO and CH-Hyg5. Further, we propose an additional amino acid residue to be responsible for the discrimination of the CH-XanB2 subfamily, which catalyzes the formation of two different hydroxybenzoate regioisomers, likely in a single active site. A multiple sequence alignment shows that these three crucial amino acid positions are located in conserved motifs and can therefore be used to assign unknown chorismatases to the corresponding subfamily.

PubMed: 26247872
DOI: 10.1021/JACS.5B05559

実験手法

X-RAY DIFFRACTION (1.898 Å)