1tc2: Difference between revisions
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==TERNARY SUBSTRATE COMPLEX OF THE HYPOXANTHINE PHOSPHORIBOSYLTRANSFERASE FROM TRYPANOSOMA CRUZI== | ==TERNARY SUBSTRATE COMPLEX OF THE HYPOXANTHINE PHOSPHORIBOSYLTRANSFERASE FROM TRYPANOSOMA CRUZI== | ||
<StructureSection load='1tc2' size='340' side='right' caption='[[1tc2]], [[Resolution|resolution]] 1.81Å' scene=''> | <StructureSection load='1tc2' size='340' side='right' caption='[[1tc2]], [[Resolution|resolution]] 1.81Å' scene=''> | ||
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=7HP:7-HYDROXY-PYRAZOLO[4,3-D]PYRIMIDINE'>7HP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=PRP:ALPHA-PHOSPHORIBOSYLPYROPHOSPHORIC+ACID'>PRP</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=7HP:7-HYDROXY-PYRAZOLO[4,3-D]PYRIMIDINE'>7HP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=PRP:ALPHA-PHOSPHORIBOSYLPYROPHOSPHORIC+ACID'>PRP</scene></td></tr> | ||
<tr id='activity'><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 id='activity'><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 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=1tc2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1tc2 OCA], [http://pdbe.org/1tc2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1tc2 RCSB], [http://www.ebi.ac.uk/pdbsum/1tc2 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=1tc2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1tc2 OCA], [http://pdbe.org/1tc2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1tc2 RCSB], [http://www.ebi.ac.uk/pdbsum/1tc2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1tc2 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Evolutionary Conservation == | == Evolutionary Conservation == | ||
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Check<jmol> | Check<jmol> | ||
<jmolCheckbox> | <jmolCheckbox> | ||
<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/tc/1tc2_consurf.spt"</scriptWhenChecked> | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/tc/1tc2_consurf.spt"</scriptWhenChecked> | ||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | ||
<text>to colour the structure by Evolutionary Conservation</text> | <text>to colour the structure by Evolutionary Conservation</text> | ||
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</div> | </div> | ||
<div class="pdbe-citations 1tc2" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 1tc2" style="background-color:#fffaf0;"></div> | ||
== References == | == References == | ||
<references/> | <references/> | ||
Revision as of 21:40, 24 January 2018
TERNARY SUBSTRATE COMPLEX OF THE HYPOXANTHINE PHOSPHORIBOSYLTRANSFERASE FROM TRYPANOSOMA CRUZITERNARY SUBSTRATE COMPLEX OF THE HYPOXANTHINE PHOSPHORIBOSYLTRANSFERASE FROM TRYPANOSOMA CRUZI
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 PubMedHypoxanthine phosphoribosyltransferase (HPRT) salvages 6-oxopurine bases in the nucleotide metabolic pathway. The 1.8 A crystal structure of an asymmetric dimer of the HPRT from the protozoan parasite Trypanosoma cruzi was determined in a ternary complex with the primary substrate phosphoribosylpyrophosphate (PRPP) and an analogue of the substrate hypoxanthine, revealing both open and closed active site conformations. The ligands are positioned for in-line nucleophilic attack at the PRPP ribose C1' by two metal ions which straddle the pyrophosphate leaving group. The structure provides the first evidence for the involvement of two metal ions in the HPRT-catalyzed reaction, and structural details further suggest the mechanism may proceed via SN2-type chemistry. The closed conformation reveals the structural roles for invariant flexible loop residues Ser103 and Tyr104 and supports a role for the loop in the liberation of pyrophosphate. The pre-transition state structure is valuable for understanding the enzyme mechanism, as well as providing a foundation for antiparasite drug design efforts against T. cruzi, which causes Chagas' disease in humans. Additionally, the structure illuminates the molecular basis of three inherited mutations in the human HPRT leading to Lesch-Nyhan syndrome (D193N) or gout (S103R or S109L), as the homologous residues in the trypanosomal enzyme contribute to the previously unrecognized Mg2+ ion binding site and to the formation of the closed flexible loop, respectively. Approaching the transition state in the crystal structure of a phosphoribosyltransferase.,Focia PJ, Craig SP 3rd, Eakin AE Biochemistry. 1998 Dec 8;37(49):17120-7. PMID:9860824[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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