2ab8: Difference between revisions

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-[[Image:2ab8.gif|left|200px]]<br /><applet load="2ab8" size="450" color="white" frame="true" align="right" spinBox="true"
-caption="2ab8, resolution 1.75&Aring;" />
-'''Crystal structure of T. gondii adenosine kinase complexed with 6-methylmercaptopurine riboside and AMP-PCP'''<br />
-==Overview==
+==Crystal structure of T. gondii adenosine kinase complexed with 6-methylmercaptopurine riboside and AMP-PCP==
-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.
+<StructureSection load='2ab8' size='340' side='right'caption='[[2ab8]], [[Resolution|resolution]] 1.75&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[2ab8]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Toxoplasma_gondii Toxoplasma gondii]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2AB8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2AB8 FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.75&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACP:PHOSPHOMETHYLPHOSPHONIC+ACID+ADENYLATE+ESTER'>ACP</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=MTP:2-HYDROXYMETHYL-5-(6-METHYLSULFANYL-PURIN-9-YL)-TETRAHYDRO-FURAN-3,4-DIOL'>MTP</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2ab8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ab8 OCA], [https://pdbe.org/2ab8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2ab8 RCSB], [https://www.ebi.ac.uk/pdbsum/2ab8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2ab8 ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/ADK_TOXGO ADK_TOXGO] ATP-dependent phosphorylation of adenosine and other related nucleoside analogs to monophosphate derivatives. It is a key purine metabolic enzyme in the opportunistic parasitic protozoan toxoplasma gondii as it cannot synthesize purines de novo.
+== Evolutionary Conservation ==
+[[Image:Consurf_key_small.gif|200px|right]]
+Check<jmol>
+  <jmolCheckbox>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ab/2ab8_consurf.spt"</scriptWhenChecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
+    <text>to colour the structure by Evolutionary Conservation</text>
+  </jmolCheckbox>
+</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2ab8 ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+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==
+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<ref>PMID:17242506</ref>
-AB8 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, MTP 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://ispc.weizmann.ac.il/oca-bin/ocashort?id=2AB8 OCA].
-==Reference==
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-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://ispc.weizmann.ac.il//pmbin/getpm?pmid=17242506 17242506]
+</div>
-[[Category: Adenosine kinase]]
+<div class="pdbe-citations 2ab8" style="background-color:#fffaf0;"></div>
-[[Category: Single protein]]
+==See Also==
+*[[Adenosine kinase 3D structures|Adenosine kinase 3D structures]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Large Structures]]
 [[Category: Toxoplasma gondii]]
-[[Category: Ealick, S.E.]]
+[[Category: Ealick SE]]
-[[Category: Kouni, M.H.el.]]
+[[Category: Zhang Y]]
-[[Category: Zhang, Y.]]
+[[Category: El Kouni MH]]
-[[Category: ACP]]
-[[Category: CL]]
-[[Category: MTP]]
-[[Category: NA]]
-[[Category: ribokinase fold; alpha/beta; intermediate conformation]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Wed Nov 21 08:01:59 2007''