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1bzy

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{{STRUCTURE_1bzy| PDB=1bzy | SCENE= }}
 
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===HUMAN HGPRTASE WITH TRANSITION STATE INHIBITOR===
 
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{{ABSTRACT_PUBMED_10360366}}
 
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==Disease==
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==HUMAN HGPRTASE WITH TRANSITION STATE INHIBITOR==
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[[http://www.uniprot.org/uniprot/HPRT_HUMAN HPRT_HUMAN]] Defects in HPRT1 are the cause of Lesch-Nyhan syndrome (LNS) [MIM:[http://omim.org/entry/300322 300322]]. LNS is characterized by complete lack of enzymatic activity that results in hyperuricemia, choreoathetosis, mental retardation, and compulsive self-mutilation.<ref>PMID:6853716</ref><ref>PMID:3384338</ref><ref>PMID:3265398</ref><ref>PMID:2910902</ref><ref>PMID:2347587</ref><ref>PMID:2358296</ref><ref>PMID:2246854</ref><ref>PMID:2071157</ref><ref>PMID:7627191</ref><ref>PMID:9452051</ref> Defects in HPRT1 are the cause of gout HPRT-related (GOUT-HPRT) [MIM:[http://omim.org/entry/300323 300323]]; also known as HPRT-related gout or Kelley-Seegmiller syndrome. Gout is characterized by partial enzyme activity and hyperuricemia.<ref>PMID:6853490</ref><ref>PMID:6572373</ref><ref>PMID:6706936</ref><ref>PMID:3358423</ref><ref>PMID:3198771</ref><ref>PMID:2909537</ref>[:]
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<StructureSection load='1bzy' size='340' side='right'caption='[[1bzy]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1bzy]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. The July 2012 RCSB PDB [https://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''Hypoxanthine-guanine phosphoribosyltransferase (HGPRT)'' by David Goodsell is [https://dx.doi.org/10.2210/rcsb_pdb/mom_2012_7 10.2210/rcsb_pdb/mom_2012_7]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1BZY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1BZY FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=IMU:PHOSPHORIC+ACID+MONO-[5-(2-AMINO-4-OXO-4,5-DIHYDRO-3H-PYRROLO[3,2-D]PYRIMIDIN-7-YL)-3,4-DIHYDROXY-PYRROLIDIN-2-YLMETHYL]+ESTER'>IMU</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=POP:PYROPHOSPHATE+2-'>POP</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1bzy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1bzy OCA], [https://pdbe.org/1bzy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1bzy RCSB], [https://www.ebi.ac.uk/pdbsum/1bzy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1bzy ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[https://www.uniprot.org/uniprot/HPRT_HUMAN HPRT_HUMAN] Defects in HPRT1 are the cause of Lesch-Nyhan syndrome (LNS) [MIM:[https://omim.org/entry/300322 300322]. LNS is characterized by complete lack of enzymatic activity that results in hyperuricemia, choreoathetosis, mental retardation, and compulsive self-mutilation.<ref>PMID:6853716</ref> <ref>PMID:3384338</ref> <ref>PMID:3265398</ref> <ref>PMID:2910902</ref> <ref>PMID:2347587</ref> <ref>PMID:2358296</ref> <ref>PMID:2246854</ref> <ref>PMID:2071157</ref> <ref>PMID:7627191</ref> <ref>PMID:9452051</ref> Defects in HPRT1 are the cause of gout HPRT-related (GOUT-HPRT) [MIM:[https://omim.org/entry/300323 300323]; also known as HPRT-related gout or Kelley-Seegmiller syndrome. Gout is characterized by partial enzyme activity and hyperuricemia.<ref>PMID:6853490</ref> <ref>PMID:6572373</ref> <ref>PMID:6706936</ref> <ref>PMID:3358423</ref> <ref>PMID:3198771</ref> <ref>PMID:2909537</ref> [:]
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== Function ==
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[https://www.uniprot.org/uniprot/HPRT_HUMAN HPRT_HUMAN] Converts guanine to guanosine monophosphate, and hypoxanthine to inosine monophosphate. Transfers the 5-phosphoribosyl group from 5-phosphoribosylpyrophosphate onto the purine. Plays a central role in the generation of purine nucleotides through the purine salvage pathway.
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/bz/1bzy_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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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=1bzy ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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The structure of human HGPRT bound to the transition-state analog immucillinGP and Mg2+-pyrophosphate has been determined to 2.0 A resolution. ImmucillinGP was designed as a stable analog with the stereoelectronic features of the transition state. Bound inhibitor at the catalytic site indicates that the oxocarbenium ion of the transition state is stabilized by neighboring-group participation from MgPPi and O5'. A short hydrogen bond forms between Asp 137 and the purine ring analog. Two Mg2+ ions sandwich the pyrophosphate and contact both hydroxyls of the ribosyl analog. The transition-state analog is shielded from bulk solvent by a catalytic loop that moves approximately 25 A to cover the active site and becomes an ordered antiparallel beta-sheet.
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==Function==
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The 2.0 A structure of human hypoxanthine-guanine phosphoribosyltransferase in complex with a transition-state analog inhibitor.,Shi W, Li CM, Tyler PC, Furneaux RH, Grubmeyer C, Schramm VL, Almo SC Nat Struct Biol. 1999 Jun;6(6):588-93. PMID:10360366<ref>PMID:10360366</ref>
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[[http://www.uniprot.org/uniprot/HPRT_HUMAN HPRT_HUMAN]] Converts guanine to guanosine monophosphate, and hypoxanthine to inosine monophosphate. Transfers the 5-phosphoribosyl group from 5-phosphoribosylpyrophosphate onto the purine. Plays a central role in the generation of purine nucleotides through the purine salvage pathway.
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==About this Structure==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[1bzy]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1BZY OCA].
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</div>
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<div class="pdbe-citations 1bzy" style="background-color:#fffaf0;"></div>
==See Also==
==See Also==
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*[[Phosphoribosyltransferase|Phosphoribosyltransferase]]
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*[[Phosphoribosyltransferase 3D structures|Phosphoribosyltransferase 3D structures]]
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== References ==
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==Reference==
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<references/>
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<ref group="xtra">PMID:010360366</ref><references group="xtra"/><references/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Hypoxanthine phosphoribosyltransferase]]
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[[Category: Large Structures]]
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[[Category: Almo, S C.]]
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[[Category: RCSB PDB Molecule of the Month]]
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[[Category: Furneaux, R H.]]
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[[Category: Almo SC]]
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[[Category: Grubmeyer, C.]]
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[[Category: Furneaux RH]]
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[[Category: Li, C.]]
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[[Category: Grubmeyer C]]
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[[Category: Schramm, V L.]]
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[[Category: Li C]]
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[[Category: Shi, W.]]
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[[Category: Schramm VL]]
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[[Category: Tyler, P C.]]
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[[Category: Shi W]]
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[[Category: Hgprt]]
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[[Category: Tyler PC]]
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[[Category: Immucillin]]
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[[Category: Lesch-nyhan]]
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[[Category: Magnesium]]
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[[Category: Neighboring group participation]]
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[[Category: Oxocarbenium ion]]
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[[Category: Phosphoribosyltransferase]]
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[[Category: Pyrophosphate]]
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[[Category: Transition state]]
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Current revision

HUMAN HGPRTASE WITH TRANSITION STATE INHIBITOR

PDB ID 1bzy

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