2jaq

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2jaq, resolution 2.30Å

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STRUCTURE OF DEOXYADENOSINE KINASE FROM M. MYCOIDES WITH BOUND DCTP

Overview

Deoxyribonucleoside kinases (dNKs) catalyze the transfer of a phosphoryl, group from ATP to a deoxyribonucleoside (dN), a key step in DNA precursor, synthesis. Recently structural information concerning dNKs has been, obtained, but no structure of a bacterial dCK/dGK enzyme is known. Here we, report the structure of such an enzyme, represented by deoxyadenosine, kinase from Mycoplasma mycoides subsp. mycoides small colony type, (Mm-dAK). Superposition of Mm-dAK with its human counterpart's, deoxyguanosine kinase (dGK) and deoxycytidine kinase (dCK) reveals that, the overall structures are very similar with a few amino acid alterations, in the proximity of the active site. To investigate the substrate, specificity, Mm-dAK has been crystallized in complex with dATP and dCTP, as well as the products dCMP and dCDP. Both dATP and dCTP bind to the, enzyme in a feedback-inhibitory manner with the dN part in the, deoxyribonucleoside binding site and the triphosphates in the P-loop., Substrate specificity studies with clinically important nucleoside analogs, as well as several phosphate donors were performed. Thus, in this study we, combine structural and kinetic data to gain a better understanding of the, substrate specificity of the dCK/dGK family of enzymes. The structure of, Mm-dAK provides a starting point for making new anti bacterial agents, against pathogenic bacteria.

About this Structure

2JAQ is a Single protein structure of sequence from Mycoplasma mycoides subsp. mycoides sc with as ligand. Known structural/functional Site: . Full crystallographic information is available from OCA.

Reference

Structure-function analysis of a bacterial deoxyadenosine kinase reveals the basis for substrate specificity., Welin M, Wang L, Eriksson S, Eklund H, J Mol Biol. 2007 Mar 9;366(5):1615-23. Epub 2006 Dec 8. PMID:17229440

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