4rhu
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structures of Mycobacterium tuberculosis 6-oxopurine phosphoribosyltransferase which is a potential target for drug development against this disease== | |
| + | <StructureSection load='4rhu' size='340' side='right'caption='[[4rhu]], [[Resolution|resolution]] 2.57Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[4rhu]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis_H37Rv Mycobacterium tuberculosis H37Rv]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4RHU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4RHU 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]] 2.573Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3QE:{[(2R)-3-(2-AMINO-6-OXO-1,6-DIHYDRO-9H-PURIN-9-YL)PROPANE-1,2-DIYL]BIS(OXYETHANE-2,1-DIYL)}BIS(PHOSPHONIC+ACID)'>3QE</scene>, <scene name='pdbligand=45T:{[(2S)-3-(2-AMINO-6-OXO-1,6-DIHYDRO-9H-PURIN-9-YL)PROPANE-1,2-DIYL]BIS(OXYETHANE-2,1-DIYL)}BIS(PHOSPHONIC+ACID)'>45T</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=4rhu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4rhu OCA], [https://pdbe.org/4rhu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4rhu RCSB], [https://www.ebi.ac.uk/pdbsum/4rhu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4rhu ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/HGPRT_MYCTU HGPRT_MYCTU] Purine salvage pathway enzyme that catalyzes the transfer of the ribosyl-5-phosphate group from 5-phospho-alpha-D-ribose 1-diphosphate (PRPP) to the N9 position of the 6-oxopurines hypoxanthine and guanine to form the corresponding ribonucleotides IMP (inosine 5'-monophosphate) and GMP (guanosine 5'-monophosphate), with the release of PPi (PubMed:19362594, PubMed:25915781). Thus, specifically recycles hypoxanthine and guanine imported from the external medium, and converts them to IMP and GMP, respectively. Cannot use xanthine as substrate (PubMed:19362594).<ref>PMID:19362594</ref> <ref>PMID:25915781</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Human tuberculosis is a chronic infectious disease affecting millions of lives. Because of emerging resistance to current medications, new therapeutic drugs are needed. One potential new target is hypoxanthine-guanine phosphoribosyltransferase (MtHGPRT), a key enzyme of the purine salvage pathway. Here, newly synthesized acyclic nucleoside phosphonates (ANPs) have been shown to be competitive inhibitors of MtHGPRT with Ki values as low as 0.69 muM. Prodrugs of these compounds arrest the growth of a virulent strain of M. tuberculosis with MIC50 values as low as 4.5 muM and possess low cytotoxicity in mammalian cells (CC50 values as high as >300 muM). In addition, the first crystal structures of MtHGPRT (2.03-2.76 A resolution) have been determined, three of these in complex with novel ANPs and one with GMP and pyrophosphate. These data provide a solid foundation for the further development of ANPs as selective inhibitors of MtHGPRT and as antituberculosis agents. | ||
| - | + | First Crystal Structures of Mycobacterium tuberculosis 6-Oxopurine Phosphoribosyltransferase: Complexes with GMP and Pyrophosphate and with Acyclic Nucleoside Phosphonates Whose Prodrugs Have Antituberculosis Activity.,Eng WS, Hockova D, Spacek P, Janeba Z, West NP, Woods K, Naesens LM, Keough DT, Guddat LW J Med Chem. 2015 May 13. PMID:25915781<ref>PMID:25915781</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| + | </div> | ||
| + | <div class="pdbe-citations 4rhu" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Phosphoribosyltransferase 3D structures|Phosphoribosyltransferase 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Mycobacterium tuberculosis H37Rv]] | ||
| + | [[Category: Eng WS]] | ||
| + | [[Category: Guddat LW]] | ||
| + | [[Category: Hockova D]] | ||
| + | [[Category: Keough DT]] | ||
| + | [[Category: Naesens LMJ]] | ||
| + | [[Category: Spacek P]] | ||
| + | [[Category: West NP]] | ||
| + | [[Category: Woods K]] | ||
Current revision
Crystal structures of Mycobacterium tuberculosis 6-oxopurine phosphoribosyltransferase which is a potential target for drug development against this disease
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