3JDW

CRYSTAL STRUCTURE AND MECHANISM OF L-ARGININE: GLYCINE AMIDINOTRANSFERASE: A MITOCHONDRIAL ENZYME INVOLVED IN CREATINE BIOSYNTHESIS

3JDW の概要

• エントリーDOI: 10.2210/pdb3jdw/pdb
• 分子名称: L-ARGININE\:GLYCINE AMIDINOTRANSFERASE, L-ornithine (3 entities in total)
• 機能のキーワード: transferase, creatine biosynthesis, catalytic triad, reaction mechanism, novel fold, fivefold pseudosymmetry
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Mitochondrion inner membrane; Peripheral membrane protein; Intermembrane side (Potential): P50440
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 48653.53

構造登録者

Humm, A.,Fritsche, E.,Steinbacher, S.,Huber, R. (登録日: 1997-01-24, 公開日: 1998-01-28, 最終更新日: 2024-05-22)

主引用文献

Humm, A.,Fritsche, E.,Steinbacher, S.,Huber, R.
Crystal structure and mechanism of human L-arginine:glycine amidinotransferase: a mitochondrial enzyme involved in creatine biosynthesis.
EMBO J., 16:3373-3385, 1997

PubMed Abstract: L-arginine:glycine amidinotransferase (AT) catalyses the committed step in creatine biosynthesis by formation of guanidinoacetic acid, the immediate precursor of creatine. We have determined the crystal structure of the recombinant human enzyme by multiple isomorphous replacement at 1.9 A resolution. A telluromethionine derivative was used in sequence assignment. The structure of AT reveals a new fold with 5-fold pseudosymmetry of circularly arranged betabeta alphabeta-modules. These enclose the active site compartment, which is accessible only through a narrow channel. The overall structure resembles a basket with handles that are formed from insertions into the betabeta alphabeta-modules. Binding of L-ornithine, a product inhibitor, reveals a marked induced-fit mechanism, with a loop at the active site entrance changing its conformation accompanied by a shift of an alpha-helix by -4 A. Binding of the arginine educt to the inactive mutant C407A shows a similar mode of binding. A reaction mechanism with a catalytic triad Cys-His-Asp is proposed on the basis of substrate and product bound states.

PubMed: 9218780
DOI: 10.1093/emboj/16.12.3373

実験手法

X-RAY DIFFRACTION (2.4 Å)