1lii: Difference between revisions

Revision as of 14:45, 21 February 2008

STRUCTURE OF T. GONDII ADENOSINE KINASE BOUND TO ADENOSINE 2 AND AMP-PCP

OverviewOverview

Adenosine kinase (AK) is a key purine metabolic enzyme from the opportunistic parasitic protozoan Toxoplasma gondii and belongs to the family of carbohydrate kinases that includes ribokinase. To understand the catalytic mechanism of AK, we determined the structures of the T. gondii apo AK, AK:adenosine complex and the AK:adenosine:AMP-PCP complex to 2.55 A, 2.50 A and 1.71 A resolution, respectively. These structures reveal a novel catalytic mechanism that involves an adenosine-induced domain rotation of 30 degrees and a newly described anion hole (DTXGAGD), requiring a helix-to-coil conformational change that is induced by ATP binding. Nucleotide binding also evokes a coil-to-helix transition that completes the formation of the ATP binding pocket. A conserved dipeptide, Gly68-Gly69, which is located at the bottom of the adenosine-binding site, functions as the switch for domain rotation. The synergistic structural changes that occur upon substrate binding sequester the adenosine and the ATP gamma phosphate from solvent and optimally position the substrates for catalysis. Finally, the 1.84 A resolution structure of an AK:7-iodotubercidin:AMP-PCP complex reveals the basis for the higher affinity binding of this prodrug over adenosine and thus provides a scaffold for the design of new inhibitors and subversive substrates that target the T. gondii AK.

About this StructureAbout this Structure

1LII is a Single protein structure of sequence from Toxoplasma gondii with , , and as ligands. This structure supersedes the now removed PDB entry 1DGY. Active as Adenosine kinase, with EC number 2.7.1.20 Full crystallographic information is available from OCA.

ReferenceReference

Crystal structures of Toxoplasma gondii adenosine kinase reveal a novel catalytic mechanism and prodrug binding., Schumacher MA, Scott DM, Mathews II, Ealick SE, Roos DS, Ullman B, Brennan RG, J Mol Biol. 2000 May 19;298(5):875-93. PMID:10801355

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 '''STRUCTURE OF T. GONDII ADENOSINE KINASE BOUND TO ADENOSINE 2 AND AMP-PCP'''<br />
 ==Overview==
-Adenosine kinase (AK) is a key purine metabolic enzyme from the, opportunistic parasitic protozoan Toxoplasma gondii and belongs to the, family of carbohydrate kinases that includes ribokinase. To understand the, catalytic mechanism of AK, we determined the structures of the T. gondii, apo AK, AK:adenosine complex and the AK:adenosine:AMP-PCP complex to 2.55, A, 2.50 A and 1.71 A resolution, respectively. These structures reveal a, novel catalytic mechanism that involves an adenosine-induced domain, rotation of 30 degrees and a newly described anion hole (DTXGAGD), requiring a helix-to-coil conformational change that is induced by ATP, binding. Nucleotide binding also evokes a coil-to-helix transition that, completes the formation of the ATP binding pocket. A conserved dipeptide, Gly68-Gly69, which is located at the bottom of the adenosine-binding site, functions as the switch for domain rotation. The synergistic structural, changes that occur upon substrate binding sequester the adenosine and the, ATP gamma phosphate from solvent and optimally position the substrates for, catalysis. Finally, the 1.84 A resolution structure of an, AK:7-iodotubercidin:AMP-PCP complex reveals the basis for the higher, affinity binding of this prodrug over adenosine and thus provides a, scaffold for the design of new inhibitors and subversive substrates that, target the T. gondii AK.
+Adenosine kinase (AK) is a key purine metabolic enzyme from the opportunistic parasitic protozoan Toxoplasma gondii and belongs to the family of carbohydrate kinases that includes ribokinase. To understand the catalytic mechanism of AK, we determined the structures of the T. gondii apo AK, AK:adenosine complex and the AK:adenosine:AMP-PCP complex to 2.55 A, 2.50 A and 1.71 A resolution, respectively. These structures reveal a novel catalytic mechanism that involves an adenosine-induced domain rotation of 30 degrees and a newly described anion hole (DTXGAGD), requiring a helix-to-coil conformational change that is induced by ATP binding. Nucleotide binding also evokes a coil-to-helix transition that completes the formation of the ATP binding pocket. A conserved dipeptide, Gly68-Gly69, which is located at the bottom of the adenosine-binding site, functions as the switch for domain rotation. The synergistic structural changes that occur upon substrate binding sequester the adenosine and the ATP gamma phosphate from solvent and optimally position the substrates for catalysis. Finally, the 1.84 A resolution structure of an AK:7-iodotubercidin:AMP-PCP complex reveals the basis for the higher affinity binding of this prodrug over adenosine and thus provides a scaffold for the design of new inhibitors and subversive substrates that target the T. gondii AK.
 ==About this Structure==
-LII 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 MG, CL, ADN and ACP as [http://en.wikipedia.org/wiki/ligands ligands]. This structure superseeds the now removed PDB entry 1DGY. 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://ispc.weizmann.ac.il/oca-bin/ocashort?id=1LII OCA].
+LII 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=MG:'>MG</scene>, <scene name='pdbligand=CL:'>CL</scene>, <scene name='pdbligand=ADN:'>ADN</scene> and <scene name='pdbligand=ACP:'>ACP</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. This structure supersedes the now removed PDB entry 1DGY. 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=1LII OCA].
 ==Reference==
@@ Line 14: / Line 14: @@
 [[Category: Single protein]]
 [[Category: Toxoplasma gondii]]
-[[Category: Brennan, R.G.]]
+[[Category: Brennan, R G.]]
-[[Category: Ealick, S.E.]]
+[[Category: Ealick, S E.]]
-[[Category: Mathews, I.I.]]
+[[Category: Mathews, I I.]]
-[[Category: Roos, D.S.]]
+[[Category: Roos, D S.]]
-[[Category: Schumacher, M.A.]]
+[[Category: Schumacher, M A.]]
-[[Category: Scott, D.M.]]
+[[Category: Scott, D M.]]
 [[Category: Ullman, B.]]
 [[Category: ACP]]
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 [[Category: alpha-beta structure]]
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