1KP3

Crystal Structure of E. coli Argininosuccinate Synthetase in Complex with ATP and Citrulline

1KP3 の概要

• エントリーDOI: 10.2210/pdb1kp3/pdb
• 関連するPDBエントリー: 1K92 1K97 1KP2
• 分子名称: argininosuccinate synthetase, PHOSPHATE ION, ADENOSINE-5'-TRIPHOSPHATE, ... (6 entities in total)
• 機能のキーワード: n-type atp pyrophosphatase, ligase
• 由来する生物種: Escherichia coli
• 細胞内の位置: Cytoplasm (Probable): P0A6E4
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 52037.93

構造登録者

Lemke, C.T.,Howell, P.L. (登録日: 2001-12-27, 公開日: 2002-04-17, 最終更新日: 2023-11-15)

主引用文献

Lemke, C.T.,Howell, P.L.
Substrate Induced Conformational Changes in Argininosuccinate Synthetase
J.Biol.Chem., 277:13074-13081, 2002

PubMed Abstract: Argininosuccinate synthetase (AS) is the rate-limiting enzyme of both the urea and arginine-citrulline cycles. In mammals, deficiency of AS leads to citrullinemia, a debilitating and often fatal autosomal recessive urea cycle disorder, whereas its overexpression for sustained nitric oxide production via the arginine-citrulline cycle leads to the potentially fatal hypotension associated with septic and cytokine-induced circulatory shock. The crystal structures of Escherichia coli argininosuccinate synthetase (EAS) in complex with ATP and with ATP and citrulline have been determined at 2.0-A resolution. These are the first EAS structures to be solved in the presence of a nucleotide substrate and clearly identify the residues that interact with both ATP and citrulline. Two distinct conformations are revealed for ATP, both of which are believed to be catalytically relevant. In addition, comparisons of these EAS structures with those of the apoenzyme and EAS complexed with aspartate and citrulline (Lemke, C. T., and Howell, P. L. (2001) Structure (Lond.) 9, 1153-1164) provide structural evidence of ATP-induced conformational changes in the nucleotide binding domain. Combined, these structures also provide structural explanations of some of the observed kinetic properties of the enzyme and have enabled a detailed enzymatic mechanism of AS catalysis to be proposed.

PubMed: 11809762
DOI: 10.1074/jbc.M112436200

実験手法

X-RAY DIFFRACTION (2 Å)