1BX4

STRUCTURE OF HUMAN ADENOSINE KINASE AT 1.50 ANGSTROMS

Summary for 1BX4

• Entry DOI: 10.2210/pdb1bx4/pdb
• Descriptor: PROTEIN (ADENOSINE KINASE), CHLORIDE ION, MAGNESIUM ION, ... (5 entities in total)
• Functional Keywords: human adenosine kinase, transferase
• Biological source: Homo sapiens (human)
• Cellular location: Isoform 1: Nucleus . Isoform 2: Cytoplasm : P55263
• Total number of polymer chains: 1
• Total formula weight: 39433.52

Authors

Mathews, I.I.,Erion, M.D.,Ealick, S.E. (deposition date: 1998-10-13, release date: 1999-10-13, Last modification date: 2023-12-27)

Primary citation

Mathews, I.I.,Erion, M.D.,Ealick, S.E.
Structure of human adenosine kinase at 1.5 A resolution.
Biochemistry, 37:15607-15620, 1998

PubMed Abstract: 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.

PubMed: 9843365
DOI: 10.1021/bi9815445

Experimental method

X-RAY DIFFRACTION (1.5 Å)