View source for 3ggc


==Human hypoxanthine-guanine phosphoribosyltransferase in complex with 9-(2-phosphonoethoxyethyl)hypoxanthine==
<StructureSection load='3ggc' size='340' side='right'caption='[[3ggc]], [[Resolution|resolution]] 2.78&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3ggc]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3GGC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3GGC FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=H26:{2-[2-(6-OXO-1,6-DIHYDRO-9H-PURIN-9-YL)ETHOXY]ETHYL}PHOSPHONIC+ACID'>H26</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1hmp|1hmp]], [[1z7g|1z7g]], [[1d6n|1d6n]]</div></td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">HPRT, HPRT1, HPT ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Hypoxanthine_phosphoribosyltransferase Hypoxanthine phosphoribosyltransferase], with EC number [https://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=3ggc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ggc OCA], [https://pdbe.org/3ggc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3ggc RCSB], [https://www.ebi.ac.uk/pdbsum/3ggc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3ggc 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/gg/3ggc_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=3ggc ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The purine salvage enzyme hypoxanthine-guanine-xanthine phosphoribosyltransferase (HGXPRT) is essential for purine nucleotide and hence nucleic acid synthesis in the malaria parasite, Plasmodium falciparum. Acyclic nucleoside phosphonates (ANPs) are analogues of the nucleotide product of the reaction, comprising a purine base joined by a linker to a phosphonate moiety. K(i) values for 19 ANPs were determined for Pf HGXPRT and the corresponding human enzyme, HGPRT. Values for Pf HGXPRT were as low as 100 nM, with selectivity for the parasite enzyme of up to 58. Structures of human HGPRT in complex with three ANPs are reported. On binding, a large mobile loop in the free enzyme moves to partly cover the active site. For three ANPs, the IC(50) values for Pf grown in cell culture were 1, 14, and 46 microM, while the cytotoxic concentration for the first compound was 489 microM. These results provide a basis for the design of potent and selective ANP inhibitors of Pf HGXPRT as antimalarial drug leads.

Inhibition of hypoxanthine-guanine phosphoribosyltransferase by acyclic nucleoside phosphonates: a new class of antimalarial therapeutics.,Keough DT, Hockova D, Holy A, Naesens LM, Skinner-Adams TS, Jersey J, Guddat LW J Med Chem. 2009 Jul 23;52(14):4391-9. PMID:19527031<ref>PMID:19527031</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 3ggc" style="background-color:#fffaf0;"></div>

==See Also==
*[[Phosphoribosyltransferase 3D structures|Phosphoribosyltransferase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Human]]
[[Category: Hypoxanthine phosphoribosyltransferase]]
[[Category: Large Structures]]
[[Category: Guddat, L W]]
[[Category: Jersey, J]]
[[Category: Keough, D T]]
[[Category: Acyclic nucleoside phosphonate]]
[[Category: Disease mutation]]
[[Category: Glycosyltransferase]]
[[Category: Gout]]
[[Category: Magnesium]]
[[Category: Metal-binding]]
[[Category: Phosphoribosyltransferase]]
[[Category: Purine salvage]]
[[Category: Transferase]]