1fsg: Difference between revisions
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==TOXOPLASMA GONDII HYPOXANTHINE-GUANINE PHOSPHORIBOSYLTRANSFERASE COMPLEXED WITH 9-DEAZAGUANINE, ALPHA-D-5-PHOSPHORIBOSYL-1-PYROPHOSPHATE (PRPP) AND TWO MG2+ IONS== | |||
<StructureSection load='1fsg' size='340' side='right' caption='[[1fsg]], [[Resolution|resolution]] 1.05Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[1fsg]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Toxoplasma_gondii_rh Toxoplasma gondii rh]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1FSG OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1FSG FirstGlance]. <br> | |||
</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=9DG:9-DEAZAGUANINE'>9DG</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PRP:ALPHA-PHOSPHORIBOSYLPYROPHOSPHORIC+ACID'>PRP</scene><br> | |||
<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1dbr|1dbr]], [[1hmp|1hmp]], [[1qk3|1qk3]], [[1qk4|1qk4]], [[1qk5|1qk5]], [[1tc2|1tc2]], [[1bzy|1bzy]]</td></tr> | |||
<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Hypoxanthine_phosphoribosyltransferase Hypoxanthine phosphoribosyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.2.8 2.4.2.8] </span></td></tr> | |||
<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1fsg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1fsg OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1fsg RCSB], [http://www.ebi.ac.uk/pdbsum/1fsg PDBsum]</span></td></tr> | |||
<table> | |||
== 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/fs/1fsg_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/chain_selection.php?pdb_ID=2ata ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
BACKGROUND: Hypoxanthine-guanine phosphoribosyltransferases (HGPRTs) are well-recognized antiparasitic drug targets. HGPRT is also a paradigmatic representative of the phosphoribosyltransferase family of enzymes, which includes other important biosynthetic and salvage enzymes and drug targets. To better understand the reaction mechanism of this enzyme, we have crystallized HGPRT from the apicomplexan protozoan Toxoplasma gondii as a ternary complex with a substrate and a substrate analog. RESULTS: The crystal structure of T. gondii HGPRT with the substrate Mg2+-PRPP and a nonreactive substrate analog, 9-deazaguanine, bound in the active site has been determined at 1.05 A resolution and refined to a free R factor of 15.4%. This structure constitutes the first atomic-resolution structure of both a phosphoribosyltransferase and the central metabolic substrate PRPP. This pre-transition state complex provides a clearer understanding of the structural basis for catalysis by HGPRT. CONCLUSIONS: Three types of substrate deformation, chief among them an unexpected C2'-endo pucker adopted by the PRPP ribose ring, raise the energy of the ground state. A cation-pi interaction between Tyr-118 and the developing oxocarbenium ion in the ribose ring helps to stabilize the transition state. Enforced substrate propinquity coupled with optimal reactive geometry for both the substrates and the active site residues with which they interact contributes to catalysis as well. | |||
Substrate deformation in a hypoxanthine-guanine phosphoribosyltransferase ternary complex: the structural basis for catalysis.,Heroux A, White EL, Ross LJ, Kuzin AP, Borhani DW Structure. 2000 Dec 15;8(12):1309-18. PMID:11188695<ref>PMID:11188695</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
==See Also== | ==See Also== | ||
*[[Phosphoribosyltransferase|Phosphoribosyltransferase]] | *[[Phosphoribosyltransferase|Phosphoribosyltransferase]] | ||
== References == | |||
== | <references/> | ||
__TOC__ | |||
</StructureSection> | |||
[[Category: Hypoxanthine phosphoribosyltransferase]] | [[Category: Hypoxanthine phosphoribosyltransferase]] | ||
[[Category: Toxoplasma gondii rh]] | [[Category: Toxoplasma gondii rh]] | ||
Revision as of 14:47, 3 October 2014
TOXOPLASMA GONDII HYPOXANTHINE-GUANINE PHOSPHORIBOSYLTRANSFERASE COMPLEXED WITH 9-DEAZAGUANINE, ALPHA-D-5-PHOSPHORIBOSYL-1-PYROPHOSPHATE (PRPP) AND TWO MG2+ IONSTOXOPLASMA GONDII HYPOXANTHINE-GUANINE PHOSPHORIBOSYLTRANSFERASE COMPLEXED WITH 9-DEAZAGUANINE, ALPHA-D-5-PHOSPHORIBOSYL-1-PYROPHOSPHATE (PRPP) AND TWO MG2+ IONS
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 PubMedBACKGROUND: Hypoxanthine-guanine phosphoribosyltransferases (HGPRTs) are well-recognized antiparasitic drug targets. HGPRT is also a paradigmatic representative of the phosphoribosyltransferase family of enzymes, which includes other important biosynthetic and salvage enzymes and drug targets. To better understand the reaction mechanism of this enzyme, we have crystallized HGPRT from the apicomplexan protozoan Toxoplasma gondii as a ternary complex with a substrate and a substrate analog. RESULTS: The crystal structure of T. gondii HGPRT with the substrate Mg2+-PRPP and a nonreactive substrate analog, 9-deazaguanine, bound in the active site has been determined at 1.05 A resolution and refined to a free R factor of 15.4%. This structure constitutes the first atomic-resolution structure of both a phosphoribosyltransferase and the central metabolic substrate PRPP. This pre-transition state complex provides a clearer understanding of the structural basis for catalysis by HGPRT. CONCLUSIONS: Three types of substrate deformation, chief among them an unexpected C2'-endo pucker adopted by the PRPP ribose ring, raise the energy of the ground state. A cation-pi interaction between Tyr-118 and the developing oxocarbenium ion in the ribose ring helps to stabilize the transition state. Enforced substrate propinquity coupled with optimal reactive geometry for both the substrates and the active site residues with which they interact contributes to catalysis as well. Substrate deformation in a hypoxanthine-guanine phosphoribosyltransferase ternary complex: the structural basis for catalysis.,Heroux A, White EL, Ross LJ, Kuzin AP, Borhani DW Structure. 2000 Dec 15;8(12):1309-18. PMID:11188695[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences |
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