1k92
From Proteopedia
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Crystal Structure of Uncomplexed E. coli Argininosuccinate Synthetase
Overview
BACKGROUND: 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. RESULTS: The crystal structure of E. coli AS (EAS) has, been determined by the use of selenomethionine incorporation and MAD, phasing. The structure has been refined at 1.6 A resolution in the absence, of its substrates and at 2.0 A in the presence of aspartate and citrulline, (EAS*CIT+ASP). Each monomer of this tetrameric protein has two structural, domains: a nucleotide binding domain similar to that of the "N-type" ATP, pyrophosphatase class of enzymes, and a novel catalytic/multimerization, domain. The EAS*CIT+ASP structure clearly describes the binding of, citrulline at the cleft between the two domains and of aspartate to a loop, of the nucleotide binding domain, whereas homology modeling with the, N-type ATP pyrophosphatases has provided the location of ATP binding., CONCLUSIONS: The first three-dimensional structures of AS are reported., The fold of the nucleotide binding domain confirms AS as the fourth, structurally defined member of the N-type ATP pyrophosphatases. The, structures identify catalytically important residues and suggest the, requirement for a conformational change during the catalytic cycle., Sequence similarity between the bacterial and human enzymes has been used, for providing insight into the structural and functional effects of, observed clinical mutations.
About this Structure
1K92 is a Single protein structure of sequence from Escherichia coli with SO4 and GOL as ligands. Active as Argininosuccinate synthase, with EC number 6.3.4.5 Full crystallographic information is available from OCA.
Reference
The 1.6 A crystal structure of E. coli argininosuccinate synthetase suggests a conformational change during catalysis., Lemke CT, Howell PL, Structure. 2001 Dec;9(12):1153-64. PMID:11738042
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