1e19
From Proteopedia
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STRUCTURE OF THE CARBAMATE KINASE-LIKE CARBAMOYL PHOSPHATE SYNTHETASE FROM THE HYPERTHERMOPHILIC ARCHAEON PYROCOCCUS FURIOSUS BOUND TO ADP
Overview
Carbamoyl phosphate (CP), an essential precursor of arginine and the, pyrimidine bases, is synthesized by CP synthetase (CPS) in three steps., The last step, the phosphorylation of carbamate, is also catalyzed by, carbamate kinase (CK), an enzyme used by microorganisms to produce ATP, from ADP and CP. Although the recently determined structures of CPS and CK, show no obvious mutual similarities, a CK-like CPS reported in, hyperthermophilic archaea was postulated to be a missing link in the, evolution of CP biosynthesis. The 1.5 A resolution structure of this, enzyme from Pyrococcus furiosus shows both a subunit topology and a, homodimeric molecular organization, with a 16-stranded open beta-sheet, core surrounded by alpha-helices, similar to those in CK. However, the, pyrococcal enzyme exhibits many solvent-accessible ion-pairs, an, extensive, strongly hydrophobic, intersubunit surface, and presents a, bound ADP molecule, which does not dissociate at 22 degrees C from the, enzyme. The ADP nucleotide is sequestered in a ridge formed over the, C-edge of the core sheet, at the bottom of a large cavity, with the purine, ring enclosed in a pocket specific for adenine. Overall, the enzyme, structure is ill-suited for catalyzing the characteristic three-step, reaction of CPS and supports the view that the CK-like CPS is in fact a, highly thermostable and very slow (at 37 degrees C) CK that, in the, extreme environment of P. furiosus, may have the new function of making, rather than using, CP. The thermostability of the enzyme may result from, the extension of the hydrophobic intersubunit contacts and from the large, number of exposed ion-pairs, some of which form ion-pair networks across, several secondary structure elements in each enzyme subunit. The structure, provides the first information on substrate binding and catalysis in CKs, and suggests that the slow rate at 37 degrees C is possibly a consequence, of slow product dissociation.
About this Structure
1E19 is a Single protein structure of sequence from Pyrococcus furiosus with MG and ADP as ligands. Active as Carbamate kinase, with EC number 2.7.2.2 Full crystallographic information is available from OCA.
Reference
The 1.5 A resolution crystal structure of the carbamate kinase-like carbamoyl phosphate synthetase from the hyperthermophilic Archaeon pyrococcus furiosus, bound to ADP, confirms that this thermostable enzyme is a carbamate kinase, and provides insight into substrate binding and stability in carbamate kinases., Ramon-Maiques S, Marina A, Uriarte M, Fita I, Rubio V, J Mol Biol. 2000 Jun 2;299(2):463-76. PMID:10860751
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