1KP2

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

Summary for 1KP2

• Entry DOI: 10.2210/pdb1kp2/pdb
• Related: 1k92 1k97 1kp3
• Descriptor: argininosuccinate synthetase, PHOSPHATE ION, ADENOSINE-5'-TRIPHOSPHATE, ... (5 entities in total)
• Functional Keywords: n-type atp pyrophosphatase, ligase
• Biological source: Escherichia coli
• Cellular location: Cytoplasm (Probable): P0A6E4
• Total number of polymer chains: 1
• Total formula weight: 51818.43

Authors

Lemke, C.T.,Howell, P.L. (deposition date: 2001-12-27, release date: 2002-04-17, Last modification date: 2023-08-16)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2 Å)