1fsg: Difference between revisions

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-[[Image:1fsg.gif|left|200px]]<br /><applet load="1fsg" size="450" color="white" frame="true" align="right" spinBox="true"
-caption="1fsg, resolution 1.05&Aring;" />
-'''TOXOPLASMA GONDII HYPOXANTHINE-GUANINE PHOSPHORIBOSYLTRANSFERASE COMPLEXED WITH 9-DEAZAGUANINE, ALPHA-D-5-PHOSPHORIBOSYL-1-PYROPHOSPHATE (PRPP) AND TWO MG2+ IONS'''<br />
-==Overview==
+==TOXOPLASMA GONDII HYPOXANTHINE-GUANINE PHOSPHORIBOSYLTRANSFERASE COMPLEXED WITH 9-DEAZAGUANINE, ALPHA-D-5-PHOSPHORIBOSYL-1-PYROPHOSPHATE (PRPP) AND TWO MG2+ IONS==
-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.
+<StructureSection load='1fsg' size='340' side='right'caption='[[1fsg]], [[Resolution|resolution]] 1.05&Aring;' scene=''>
+== Structural highlights ==
+<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='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='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='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>
+</table>
+== Function ==
+[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 ==
+[[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/main_output.php?pdb_ID=1fsg ConSurf].
+<div style="clear:both"></div>
-==About this Structure==
+==See Also==
-FSG 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 MG, PRP and 9DG as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1FSG OCA].
+*[[Phosphoribosyltransferase 3D structures|Phosphoribosyltransferase 3D structures]]
+== References ==
-==Reference==
+<references/>
-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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=11188695 11188695]
+__TOC__
-[[Category: Hypoxanthine phosphoribosyltransferase]]
+</StructureSection>
-[[Category: Single protein]]
+[[Category: Large Structures]]
-[[Category: Toxoplasma gondii]]
+[[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: 9DG]]
-[[Category: MG]]
-[[Category: PRP]]
-[[Category: glycosyltransferase]]
-[[Category: purine salvage]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Nov 20 15:14:19 2007''