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{{STRUCTURE_1bzy|  PDB=1bzy  |  SCENE=  }}
===HUMAN HGPRTASE WITH TRANSITION STATE INHIBITOR===
{{ABSTRACT_PUBMED_10360366}}


==Disease==
==HUMAN HGPRTASE WITH TRANSITION STATE INHIBITOR==
[[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>[:]  
<StructureSection load='1bzy' size='340' side='right'caption='[[1bzy]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
== Structural highlights ==
<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>
</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>
<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>
<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>
</table>
== Disease ==
[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> [:]
== Function ==
[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.
== 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/bz/1bzy_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=1bzy ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
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.


==Function==
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>
[[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.  


==About this Structure==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
[[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].
</div>
<div class="pdbe-citations 1bzy" style="background-color:#fffaf0;"></div>


==See Also==
==See Also==
*[[Phosphoribosyltransferase|Phosphoribosyltransferase]]
*[[Phosphoribosyltransferase 3D structures|Phosphoribosyltransferase 3D structures]]
 
== References ==
==Reference==
<references/>
<ref group="xtra">PMID:010360366</ref><references group="xtra"/><references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Hypoxanthine phosphoribosyltransferase]]
[[Category: Large Structures]]
[[Category: Almo, S C.]]
[[Category: RCSB PDB Molecule of the Month]]
[[Category: Furneaux, R H.]]
[[Category: Almo SC]]
[[Category: Grubmeyer, C.]]
[[Category: Furneaux RH]]
[[Category: Li, C.]]
[[Category: Grubmeyer C]]
[[Category: Schramm, V L.]]
[[Category: Li C]]
[[Category: Shi, W.]]
[[Category: Schramm VL]]
[[Category: Tyler, P C.]]
[[Category: Shi W]]
[[Category: Hgprt]]
[[Category: Tyler PC]]
[[Category: Immucillin]]
[[Category: Lesch-nyhan]]
[[Category: Magnesium]]
[[Category: Neighboring group participation]]
[[Category: Oxocarbenium ion]]
[[Category: Phosphoribosyltransferase]]
[[Category: Pyrophosphate]]
[[Category: Transition state]]
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