2aa0
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(New page: 200px<br /><applet load="2aa0" size="450" color="white" frame="true" align="right" spinBox="true" caption="2aa0, resolution 1.75Å" /> '''Crystal structure of...)
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Revision as of 05:53, 21 November 2007
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Crystal structure of T. gondii adenosine kinase complexed with 6-methylmercaptopurine riboside
Overview
Adenosine kinase (AK) is a key enzyme in purine metabolism in the, ubiquitous intracellular parasite Toxoplasma gondii and is a potential, chemotherapeutic target for the treatment of T. gondii infections. To, better understand the structure-activity relationship of 6-substituted, purine ribosides, the structures of the T. gondii, AK-N6,N6-dimethyladenosine (DMA) complex, the AK-DMA-AMP-PCP complex, the, AK-6-methyl mercaptopurine riboside (MMPR) complex and the AK-MMPR-AMP-PCP, complex were determined to 1.35, 1.35, 1.75 and 1.75 A resolution, respectively. These structures reveal a conformation intermediate between, open and closed, with a small lid-domain rotation of 12 degrees . Residues, Gly143-X-X-Gly146 undergo torsional changes upon substrate binding, which, together with a Gly68-Gly69 switch induces a hinge bending of the lid, domain. The intermediate conformation suggests that ATP binding is, independent of adenosine binding. Orienting the gamma-phosphate group of, ATP into the optimal catalytic position may be the last step before the, onset of chemical catalysis and may require the translocation of Arg136, following the complete closure of the lid domain. 6-Substituted, purine-nucleoside analogs are accommodated in a hydrophobic cavity., Modification at the N6 or C6 position of the nucleoside would affect the, interactions with the surrounding residues and the binding affinity.
About this Structure
2AA0 is a Single protein structure of sequence from Toxoplasma gondii with CL, NA, ACT and MTP as ligands. Active as Adenosine kinase, with EC number 2.7.1.20 Full crystallographic information is available from OCA.
Reference
Substrate analogs induce an intermediate conformational change in Toxoplasma gondii adenosine kinase., Zhang Y, El Kouni MH, Ealick SE, Acta Crystallogr D Biol Crystallogr. 2007 Feb;63(Pt 2):126-34. Epub 2007, Jan 16. PMID:17242506
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