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| | <StructureSection load='5kap' size='340' side='right'caption='[[5kap]], [[Resolution|resolution]] 2.95Å' scene=''> | | <StructureSection load='5kap' size='340' side='right'caption='[[5kap]], [[Resolution|resolution]] 2.95Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5kap]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Trybb Trybb]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5KAP OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5KAP FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5kap]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Trypanosoma_brucei_brucei Trypanosoma brucei brucei]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5KAP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5KAP FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=6RH:4-(6-OXIDANYLIDENE-1~{H}-PURIN-9-YL)BUTYLPHOSPHONIC+ACID'>6RH</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 2.95Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5kam|5kam]], [[5jsq|5jsq]], [[5jv5|5jv5]], [[5k51|5k51]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=6RH:4-(6-OXIDANYLIDENE-1~{H}-PURIN-9-YL)BUTYLPHOSPHONIC+ACID'>6RH</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">HGPRT ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=5702 TRYBB])</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=5kap FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5kap OCA], [https://pdbe.org/5kap PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5kap RCSB], [https://www.ebi.ac.uk/pdbsum/5kap PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5kap ProSAT]</span></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'>[http://proteopedia.org/fgij/fg.htm?mol=5kap FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5kap OCA], [http://pdbe.org/5kap PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5kap RCSB], [http://www.ebi.ac.uk/pdbsum/5kap PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5kap ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/HPRT_TRYBB HPRT_TRYBB]] 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 (By similarity). | + | [https://www.uniprot.org/uniprot/HPRT_TRYBB HPRT_TRYBB] 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 (By similarity). |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Hypoxanthine phosphoribosyltransferase]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Trybb]] | + | [[Category: Trypanosoma brucei brucei]] |
| - | [[Category: Guddat, L]] | + | [[Category: Guddat L]] |
| - | [[Category: Teran, D]] | + | [[Category: Teran D]] |
| - | [[Category: Complex]]
| + | |
| - | [[Category: Dimer]]
| + | |
| - | [[Category: Enzyme]]
| + | |
| - | [[Category: Inhibitor]]
| + | |
| - | [[Category: Transferase]]
| + | |
| - | [[Category: Transferase-transferase inhibitor complex]]
| + | |
| Structural highlights
Function
HPRT_TRYBB 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 (By similarity).
Publication Abstract from PubMed
Human African Trypanosomiasis (HAT) is a life-threatening infectious disease caused by the protozoan parasite, Trypanosoma brucei (Tbr). Due to the debilitating side effects of the current therapeutics and the emergence of resistance to these drugs, new medications for this disease need to be developed. One potential new drug target is 6-oxopurine phosphoribosyltransferase (PRT), an enzyme central to the purine salvage pathway and whose activity is critical for the production of the nucleotides (GMP and IMP) required for DNA/RNA synthesis within this protozoan parasite. Here, the first crystal structures of this enzyme have been determined, these in complex with GMP and IMP and with three acyclic nucleoside phosphonate (ANP) inhibitors. The Ki values for GMP and IMP are 30.5 muM and 77 muM, respectively. Two of the ANPs have Ki values considerably lower than for the nucleotides, 2.3 muM (with guanine as base) and 15.8 muM (with hypoxanthine as base). The crystal structures show that when two of the ANPs bind, they induce an unusual conformation change to the loop where the reaction product, pyrophosphate, is expected to bind. This and other structural differences between the Tbr and human enzymes suggest selective inhibitors for the Tbr enzyme can be designed.
Crystal structures and inhibition of Trypanosoma brucei hypoxanthine-guanine phosphoribosyltransferase.,Teran D, Hockova D, Cesnek M, Zikova A, Naesens L, Keough DT, Guddat LW Sci Rep. 2016 Oct 27;6:35894. doi: 10.1038/srep35894. PMID:27786284[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Teran D, Hockova D, Cesnek M, Zikova A, Naesens L, Keough DT, Guddat LW. Crystal structures and inhibition of Trypanosoma brucei hypoxanthine-guanine phosphoribosyltransferase. Sci Rep. 2016 Oct 27;6:35894. doi: 10.1038/srep35894. PMID:27786284 doi:http://dx.doi.org/10.1038/srep35894
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