2abs
From Proteopedia
(New page: 200px<br /><applet load="2abs" size="450" color="white" frame="true" align="right" spinBox="true" caption="2abs, resolution 1.10Å" /> '''Crystal structure of...) |
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| - | [[Image:2abs.gif|left|200px]]<br /><applet load="2abs" size=" | + | [[Image:2abs.gif|left|200px]]<br /><applet load="2abs" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="2abs, resolution 1.10Å" /> | caption="2abs, resolution 1.10Å" /> | ||
'''Crystal structure of T. gondii adenosine kinase complexed with AMP-PCP'''<br /> | '''Crystal structure of T. gondii adenosine kinase complexed with AMP-PCP'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The obligate intracellular parasite Toxoplasma gondii is incapable of | + | The obligate intracellular parasite Toxoplasma gondii is incapable of synthesizing purine nucleotides de novo and relies completely on purines salvaged from the host cells. Adenosine is the preferred precursor and is phosphorylated by adenosine kinase (AK), the most active enzyme in adenosine metabolism in T. gondii. AK thus represents a potential chemotherapeutic target for the treatment of T. gondii infections. The previously solved structures of unliganded AK and AK in complex with adenosine (or 7-iodotubercidin) and an ATP analog revealed a novel catalytic mechanism. A domain closure triggered by a GG switch upon adenosine binding sequesters the adenosine and gamma-phosphate of ATP from the solvent. The formation of the anion hole induced by the ATP binding completes the structural requirements for catalysis. In the current study, the structure of a binary complex of AK and the non-hydrolysable ATP analog AMP-PCP was determined to 1.1 angstroms resolution. The overall structure is similar to the apoenzyme, with an open conformation. AMP-PCP is bound in two relaxed conformations and without anchoring by Arg136. The induced anion hole is the same as that in the ternary complex AK-adenosine-AMP-PCP. This structure provides direct evidence that ATP binding at millimolar concentrations does not require adenosine binding as a prerequisite. |
==About this Structure== | ==About this Structure== | ||
| - | 2ABS is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Toxoplasma_gondii Toxoplasma gondii] with CL, NA and ACP as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Full crystallographic information is available from [http:// | + | 2ABS is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Toxoplasma_gondii Toxoplasma gondii] with <scene name='pdbligand=CL:'>CL</scene>, <scene name='pdbligand=NA:'>NA</scene> and <scene name='pdbligand=ACP:'>ACP</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2ABS OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Toxoplasma gondii]] | [[Category: Toxoplasma gondii]] | ||
| - | [[Category: Ealick, S | + | [[Category: Ealick, S E.]] |
| - | [[Category: Kouni, M | + | [[Category: Kouni, M H.el.]] |
[[Category: Zhang, Y.]] | [[Category: Zhang, Y.]] | ||
[[Category: ACP]] | [[Category: ACP]] | ||
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[[Category: ribokinase fold; alpha/beta; intermediate conformation]] | [[Category: ribokinase fold; alpha/beta; intermediate conformation]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:25:53 2008'' |
Revision as of 14:25, 21 February 2008
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Crystal structure of T. gondii adenosine kinase complexed with AMP-PCP
Overview
The obligate intracellular parasite Toxoplasma gondii is incapable of synthesizing purine nucleotides de novo and relies completely on purines salvaged from the host cells. Adenosine is the preferred precursor and is phosphorylated by adenosine kinase (AK), the most active enzyme in adenosine metabolism in T. gondii. AK thus represents a potential chemotherapeutic target for the treatment of T. gondii infections. The previously solved structures of unliganded AK and AK in complex with adenosine (or 7-iodotubercidin) and an ATP analog revealed a novel catalytic mechanism. A domain closure triggered by a GG switch upon adenosine binding sequesters the adenosine and gamma-phosphate of ATP from the solvent. The formation of the anion hole induced by the ATP binding completes the structural requirements for catalysis. In the current study, the structure of a binary complex of AK and the non-hydrolysable ATP analog AMP-PCP was determined to 1.1 angstroms resolution. The overall structure is similar to the apoenzyme, with an open conformation. AMP-PCP is bound in two relaxed conformations and without anchoring by Arg136. The induced anion hole is the same as that in the ternary complex AK-adenosine-AMP-PCP. This structure provides direct evidence that ATP binding at millimolar concentrations does not require adenosine binding as a prerequisite.
About this Structure
2ABS is a Single protein structure of sequence from Toxoplasma gondii with , and as ligands. Active as Adenosine kinase, with EC number 2.7.1.20 Full crystallographic information is available from OCA.
Reference
Structure of Toxoplasma gondii adenosine kinase in complex with an ATP analog at 1.1 angstroms resolution., Zhang Y, El Kouni MH, Ealick SE, Acta Crystallogr D Biol Crystallogr. 2006 Feb;62(Pt 2):140-5. Epub 2006, Jan 18. PMID:16421444
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