7sb7: Difference between revisions
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<StructureSection load='7sb7' size='340' side='right'caption='[[7sb7]], [[Resolution|resolution]] 2.65Å' scene=''> | <StructureSection load='7sb7' size='340' side='right'caption='[[7sb7]], [[Resolution|resolution]] 2.65Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[7sb7]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7SB7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7SB7 FirstGlance]. <br> | <table><tr><td colspan='2'>[[7sb7]] 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=7SB7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7SB7 FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=8QI:({(2S)-3-(2-amino-6-oxo-1,6-dihydro-9H-purin-9-yl)-2-[(2S)-2-hydroxy-2-phosphonoethoxy]propoxy}methyl)phosphonic+acid'>8QI</scene | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.6471663Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=8QI:({(2S)-3-(2-amino-6-oxo-1,6-dihydro-9H-purin-9-yl)-2-[(2S)-2-hydroxy-2-phosphonoethoxy]propoxy}methyl)phosphonic+acid'>8QI</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=7sb7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7sb7 OCA], [https://pdbe.org/7sb7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7sb7 RCSB], [https://www.ebi.ac.uk/pdbsum/7sb7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7sb7 ProSAT]</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=7sb7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7sb7 OCA], [https://pdbe.org/7sb7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7sb7 RCSB], [https://www.ebi.ac.uk/pdbsum/7sb7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7sb7 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
[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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</div> | </div> | ||
<div class="pdbe-citations 7sb7" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 7sb7" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Phosphoribosyltransferase 3D structures|Phosphoribosyltransferase 3D structures]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: | [[Category: Trypanosoma brucei brucei]] | ||
[[Category: | [[Category: Guddat LW]] | ||
[[Category: | [[Category: Keough DT]] | ||
Latest revision as of 19:48, 18 October 2023
Crystal structure of T. brucei hypoxanthine guanine phosphoribosyltransferase in complex with (4S,7S)-7-hydroxy-4-((guanin-9-yl)methyl)-2,5-dioxaheptan-1,7-diphosphonateCrystal structure of T. brucei hypoxanthine guanine phosphoribosyltransferase in complex with (4S,7S)-7-hydroxy-4-((guanin-9-yl)methyl)-2,5-dioxaheptan-1,7-diphosphonate
Structural highlights
FunctionHPRT_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 PubMedPathogens such as Plasmodium and Trypanosoma spp. are unable to synthesize purine nucleobases. They rely on the salvage of these purines and their nucleosides from the host cell to synthesize the purine nucleotides required for DNA/RNA production. The key enzymes in this pathway are purine phosphoribosyltransferases (PRTs). Here, we synthesized 16 novel acyclic nucleoside phosphonates, 12 with a chiral center at C-2', and eight bearing a second chiral center at C-6'. Of these, bisphosphonate (S,S)-48 is the most potent inhibitor of the Plasmodium falciparum and P. vivax 6-oxopurine PRTs and the most potent inhibitor of two Trypanosoma brucei (Tbr) 6-oxopurine PRTs yet discovered, with Ki values as low as 2 nM. Crystal structures of (S,S)-48 in complex with human and Tbr 6-oxopurine PRTs show that the inhibitor binds to the enzymes in different conformations, providing an explanation for its potency and selectivity (i.e., 35-fold in favor of the parasite enzymes). Stereo-Defined Acyclic Nucleoside Phosphonates are Selective and Potent Inhibitors of Parasite 6-Oxopurine Phosphoribosyltransferases.,Klejch T, Keough DT, King G, Dolezelova E, Cesnek M, Budesinsky M, Zikova A, Janeba Z, Guddat LW, Hockova D J Med Chem. 2022 Feb 17. doi: 10.1021/acs.jmedchem.1c01881. PMID:35175749[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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