1bx4

From Proteopedia

Revision as of 14:08, 12 November 2007

STRUCTURE OF HUMAN ADENOSINE KINASE AT 1.50 ANGSTROMS

Overview

Adenosine kinase (AK) is a key enzyme in the regulation of extracellular, adenosine and intracellular adenylate levels. Inhibitors of adenosine, kinase elevate adenosine to levels that activate nearby adenosine, receptors and produce a wide variety of therapeutically beneficial, activities. Accordingly, AK is a promising target for new analgesic, neuroprotective, and cardioprotective agents. We determined the structure, of human adenosine kinase by X-ray crystallography using MAD phasing, techniques and refined the structure to 1.5 A resolution. The enzyme, structure consisted of one large alpha/beta domain with nine beta-strands, eight alpha-helices, and one small alpha/beta-domain with five, beta-strands and two alpha-helices. The active site is formed along the, edge of the beta-sheet in the large domain while the small domain acts as, a lid to cover the upper face of the active site. The overall structure is, similar to the recently reported structure of ribokinase from Escherichia, coli [Sigrell et al. (1998) Structure 6, 183-193]. The structure of, ribokinase was determined at 1.8 A resolution and represents the first, structure of a new family of carbohydrate kinases. Two molecules of, adenosine were present in the AK crystal structure with one adenosine, molecule located in a site that matches the ribose site in ribokinase and, probably represents the substrate-binding site. The second adenosine site, overlaps the ADP site in ribokinase and probably represents the ATP site., A Mg2+ ion binding site is observed in a trough between the two adenosine, sites. The structure of the active site is consistent with the observed, substrate specificity. The active-site model suggests that Asp300 is an, important catalytic residue involved in the deprotonation of the, 5'-hydroxyl during the phosphate transfer.

About this Structure

1BX4 is a Single protein structure of sequence from Homo sapiens with CL, MG and ADN as ligands. Active as Adenosine kinase, with EC number 2.7.1.20 Structure known Active Sites: ADA and ADB. Full crystallographic information is available from OCA.

Reference

Structure of human adenosine kinase at 1.5 A resolution., Mathews II, Erion MD, Ealick SE, Biochemistry. 1998 Nov 10;37(45):15607-20. PMID:9843365

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