2JAT

Structure of deoxyadenosine kinase from M.mycoides with products dcmp and a flexible dcdp bound

Summary for 2JAT

• Entry DOI: 10.2210/pdb2jat/pdb
• Related: 2JAQ 2JAS
• Descriptor: DEOXYGUANOSINE KINASE, MAGNESIUM ION, PYROPHOSPHATE 2-, ... (5 entities in total)
• Functional Keywords: kinase, transferase, deoxyribonucleoside kinase
• Biological source: MYCOPLASMA MYCOIDES SUBSP. MYCOIDES SC
• Total number of polymer chains: 2
• Total formula weight: 49592.63

Authors

Welin, M.,Wang, L.,Eriksson, S.,Eklund, H. (deposition date: 2006-11-30, release date: 2007-01-03, Last modification date: 2023-12-13)

Primary citation

Welin, M.,Wang, L.,Eriksson, S.,Eklund, H.
Structure-Function Analysis of a Bacterial Deoxyadenosine Kinase Reveals the Basis for Substrate Specificity.
J.Mol.Biol., 366:1615-, 2007

PubMed Abstract: 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.

PubMed: 17229440
DOI: 10.1016/J.JMB.2006.12.010

Experimental method

X-RAY DIFFRACTION (2.6 Å)