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==TOXOPLASMA GONDII HYPOXANTHINE-GUANINE PHOSPHORIBOSYLTRANSFERASE COMPLEXED WITH 9-DEAZAGUANINE, ALPHA-D-5-PHOSPHORIBOSYL-1-PYROPHOSPHATE (PRPP) AND TWO MG2+ IONS==
==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]] 1.05&Aring;' scene=''>
<StructureSection load='1fsg' size='340' side='right'caption='[[1fsg]], [[Resolution|resolution]] 1.05&Aring;' scene=''>
== Structural highlights ==
== 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>
<table><tr><td colspan='2'>[[1fsg]] is a 2 chain structure with sequence from [https://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 [https://proteopedia.org/fgij/fg.htm?mol=1FSG FirstGlance]. <br>
</td></tr><tr id='ligand'><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></td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.05&#8491;</td></tr>
<tr id='related'><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 id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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></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'>[https://proteopedia.org/fgij/fg.htm?mol=1fsg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1fsg OCA], [https://pdbe.org/1fsg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1fsg RCSB], [https://www.ebi.ac.uk/pdbsum/1fsg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1fsg ProSAT]</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=1fsg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1fsg OCA], [http://pdbe.org/1fsg PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1fsg RCSB], [http://www.ebi.ac.uk/pdbsum/1fsg PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1fsg ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[[http://www.uniprot.org/uniprot/HGXR_TOXGO HGXR_TOXGO]] Catalyzes the transfer of a ribosyl phosphate group from 5-phosphoribose 1-diphosphate to the N(9) of hypoxanthine, guanine or xanthine.<ref>PMID:11188695</ref>
[https://www.uniprot.org/uniprot/HGXR_TOXGO HGXR_TOXGO] Catalyzes the transfer of a ribosyl phosphate group from 5-phosphoribose 1-diphosphate to the N(9) of hypoxanthine, guanine or xanthine.<ref>PMID:11188695</ref>  
== Evolutionary Conservation ==
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
[[Image:Consurf_key_small.gif|200px|right]]
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</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=1fsg ConSurf].
</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=1fsg ConSurf].
<div style="clear:both"></div>
<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>
==See Also==
 
*[[Phosphoribosyltransferase 3D structures|Phosphoribosyltransferase 3D structures]]
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 1fsg" style="background-color:#fffaf0;"></div>
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Hypoxanthine phosphoribosyltransferase]]
[[Category: Large Structures]]
[[Category: Toxoplasma gondii rh]]
[[Category: Toxoplasma gondii RH]]
[[Category: Borhani, D W]]
[[Category: Borhani DW]]
[[Category: Heroux, A]]
[[Category: Heroux A]]
[[Category: Kuzin, A P]]
[[Category: Kuzin AP]]
[[Category: Ross, L J]]
[[Category: Ross LJ]]
[[Category: White, E L]]
[[Category: White EL]]
[[Category: Glycosyltransferase]]
[[Category: Purine salvage]]
[[Category: Transferase]]

Latest revision as of 10:18, 7 February 2024

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

1fsg is a 2 chain structure with sequence from Toxoplasma gondii RH. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 1.05Å
Ligands:, ,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

HGXR_TOXGO Catalyzes the transfer of a ribosyl phosphate group from 5-phosphoribose 1-diphosphate to the N(9) of hypoxanthine, guanine or xanthine.[1]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

See Also

References

  1. ↑ Heroux A, White EL, Ross LJ, Kuzin AP, Borhani DW. Substrate deformation in a hypoxanthine-guanine phosphoribosyltransferase ternary complex: the structural basis for catalysis. Structure. 2000 Dec 15;8(12):1309-18. PMID:11188695

1fsg, resolution 1.05Å

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