2aa0
From Proteopedia
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| - | [[Image:2aa0.gif|left|200px]] | + | [[Image:2aa0.gif|left|200px]] |
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| - | '''Crystal structure of T. gondii adenosine kinase complexed with 6-methylmercaptopurine riboside''' | + | {{Structure |
| + | |PDB= 2aa0 |SIZE=350|CAPTION= <scene name='initialview01'>2aa0</scene>, resolution 1.75Å | ||
| + | |SITE= | ||
| + | |LIGAND= <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene> and <scene name='pdbligand=MTP:2-HYDROXYMETHYL-5-(6-METHYLSULFANYL-PURIN-9-YL)-TETRAHYDRO-FURAN-3,4-DIOL'>MTP</scene> | ||
| + | |ACTIVITY= [http://en.wikipedia.org/wiki/Adenosine_kinase Adenosine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.20 2.7.1.20] | ||
| + | |GENE= AK ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=5811 Toxoplasma gondii]) | ||
| + | }} | ||
| + | |||
| + | '''Crystal structure of T. gondii adenosine kinase complexed with 6-methylmercaptopurine riboside''' | ||
| + | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 2AA0 is a [ | + | 2AA0 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Toxoplasma_gondii Toxoplasma gondii]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2AA0 OCA]. |
==Reference== | ==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:[http:// | + | 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:[http://www.ncbi.nlm.nih.gov/pubmed/17242506 17242506] |
[[Category: Adenosine kinase]] | [[Category: Adenosine kinase]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
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[[Category: ribokinase fold; alpha/beta; intermediate conformation]] | [[Category: ribokinase fold; alpha/beta; intermediate conformation]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 15:47:11 2008'' |
Revision as of 13:47, 20 March 2008
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| , resolution 1.75Å | |||||||
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| Ligands: | , , and | ||||||
| Gene: | AK (Toxoplasma gondii) | ||||||
| Activity: | Adenosine kinase, with EC number 2.7.1.20 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
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. 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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