3ewd: Difference between revisions
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<StructureSection load='3ewd' size='340' side='right' caption='[[3ewd]], [[Resolution|resolution]] 1.90Å' scene=''> | <StructureSection load='3ewd' size='340' side='right' caption='[[3ewd]], [[Resolution|resolution]] 1.90Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[3ewd]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/ | <table><tr><td colspan='2'>[[3ewd]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Plavi Plavi]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3EWD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3EWD FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MCF:(8R)-3-(5-S-METHYL-5-THIO-BETA-D-RIBOFURANOSYL)-3,6,7,8-TETRAHYDROIMIDAZO[4,5-D][1,3]DIAZEPIN-8-OL'>MCF</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MCF:(8R)-3-(5-S-METHYL-5-THIO-BETA-D-RIBOFURANOSYL)-3,6,7,8-TETRAHYDROIMIDAZO[4,5-D][1,3]DIAZEPIN-8-OL'>MCF</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3ewc|3ewc]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3ewc|3ewc]]</td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PVX_111245 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=5855 | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PVX_111245 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=5855 PLAVI])</td></tr> | ||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Adenosine_deaminase Adenosine deaminase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.4.4 3.5.4.4] </span></td></tr> | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Adenosine_deaminase Adenosine deaminase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.4.4 3.5.4.4] </span></td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3ewd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ewd OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3ewd RCSB], [http://www.ebi.ac.uk/pdbsum/3ewd PDBsum]</span></td></tr> | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3ewd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ewd OCA], [http://pdbe.org/3ewd PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3ewd RCSB], [http://www.ebi.ac.uk/pdbsum/3ewd PDBsum]</span></td></tr> | ||
</table> | </table> | ||
== Evolutionary Conservation == | == Evolutionary Conservation == | ||
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<text>to colour the structure by Evolutionary Conservation</text> | <text>to colour the structure by Evolutionary Conservation</text> | ||
</jmolCheckbox> | </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/ | </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=3ewd ConSurf]. | ||
<div style="clear:both"></div> | <div style="clear:both"></div> | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | </div> | ||
<div class="pdbe-citations 3ewd" style="background-color:#fffaf0;"></div> | |||
==See Also== | ==See Also== | ||
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</StructureSection> | </StructureSection> | ||
[[Category: Adenosine deaminase]] | [[Category: Adenosine deaminase]] | ||
[[Category: | [[Category: Plavi]] | ||
[[Category: Almo, S C]] | [[Category: Almo, S C]] | ||
[[Category: Cassera, M B]] | [[Category: Cassera, M B]] | ||
Revision as of 10:11, 9 February 2016
Crystal structure of adenosine deaminase mutant (delta Asp172) from Plasmodium vivax in complex with MT-coformycinCrystal structure of adenosine deaminase mutant (delta Asp172) from Plasmodium vivax in complex with MT-coformycin
Structural highlights
Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedPlasmodium falciparum is a purine auxotroph requiring hypoxanthine as a key metabolic precursor. Erythrocyte adenine nucleotides are the source of the purine precursors, making adenosine deaminase (ADA) a key enzyme in the pathway of hypoxanthine formation. Methylthioadenosine (MTA) is a substrate for most malarial ADAs, but not for human ADA. The catalytic site specificity of malarial ADAs permits methylthiocoformycin (MT-coformycin) to act as a Plasmodium-specific transition state analogue with low affinity for human ADA [Tyler, P. C., Taylor, E. A., Frohlich, R. G. G., and Schramm, V. L. (2007) J. Am. Chem. Soc. 129, 6872-6879]. The structural basis for MTA and MT-coformycin specificity in malarial ADAs is the subject of speculation [Larson, E. T., et al. (2008) J. Mol. Biol. 381, 975-988]. Here, the crystal structure of ADA from Plasmodium vivax (PvADA) in a complex with MT-coformycin reveals an unprecedented binding geometry for 5'-methylthioribosyl groups in the malarial ADAs. Compared to malarial ADA complexes with adenosine or deoxycoformycin, 5'-methylthioribosyl groups are rotated 130 degrees . A hydrogen bonding network between Asp172 and the 3'-hydroxyl of MT-coformycin is essential for recognition of the 5'-methylthioribosyl group. Water occupies the 5'-hydroxyl binding site when MT-coformycin is bound. Mutagenesis of Asp172 destroys the substrate specificity for MTA and MT-coformycin. Kinetic, mutagenic, and structural analyses of PvADA and kinetic analysis of five other Plasmodium ADAs establish the unique structural basis for its specificity for MTA and MT-coformycin. Plasmodium gallinaceum ADA does not use MTA as a substrate, is not inhibited by MT-coformycin, and is missing Asp172. Treatment of P. falciparum cultures with coformycin or MT-coformycin in the presence of MTA is effective in inhibiting parasite growth. Structural and metabolic specificity of methylthiocoformycin for malarial adenosine deaminases.,Ho MC, Cassera MB, Madrid DC, Ting LM, Tyler PC, Kim K, Almo SC, Schramm VL Biochemistry. 2009 Oct 13;48(40):9618-26. PMID:19728741[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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