View source for 7scr


==Crystal structure of trypanosome brucei hypoxanthine-guanine-xanthine phosphoribzosyltransferase in complex with (4S,7S)-7-hydroxy-4-((guanin-9-yl)methyl)-2,5-dioxaheptan-1,7-diphosphonate==
<StructureSection load='7scr' size='340' side='right'caption='[[7scr]], [[Resolution|resolution]] 2.12&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7scr]] is a 6 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=7SCR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7SCR 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]] 2.1206849&#8491;</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=7scr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7scr OCA], [https://pdbe.org/7scr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7scr RCSB], [https://www.ebi.ac.uk/pdbsum/7scr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7scr ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/Q38CA1_TRYB2 Q38CA1_TRYB2] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Pathogens 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<ref>PMID:35175749</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7scr" style="background-color:#fffaf0;"></div>

==See Also==
*[[Phosphoribosyltransferase 3D structures|Phosphoribosyltransferase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Trypanosoma brucei brucei]]
[[Category: Guddat LW]]
[[Category: Keough DT]]