5e38: Difference between revisions
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==Structural basis of mapping the spontaneous mutations with 5-flourouracil in uracil phosphoribosyltransferase from Mycobacterium tuberculosis== | ==Structural basis of mapping the spontaneous mutations with 5-flourouracil in uracil phosphoribosyltransferase from Mycobacterium tuberculosis== | ||
<StructureSection load='5e38' size='340' side='right' caption='[[5e38]], [[Resolution|resolution]] 3.00Å' scene=''> | <StructureSection load='5e38' size='340' side='right' caption='[[5e38]], [[Resolution|resolution]] 3.00Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[5e38]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5E38 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5E38 FirstGlance]. <br> | <table><tr><td colspan='2'>[[5e38]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Myctu Myctu]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5E38 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5E38 FirstGlance]. <br> | ||
</td></tr><tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Uracil_phosphoribosyltransferase Uracil phosphoribosyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.2.9 2.4.2.9] </span></td></tr> | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">upp, Rv3309c, MTV016.08c ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83332 MYCTU])</td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5e38 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5e38 OCA], [http://pdbe.org/5e38 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5e38 RCSB], [http://www.ebi.ac.uk/pdbsum/5e38 PDBsum]</span></td></tr> | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Uracil_phosphoribosyltransferase Uracil phosphoribosyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.2.9 2.4.2.9] </span></td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5e38 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5e38 OCA], [http://pdbe.org/5e38 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5e38 RCSB], [http://www.ebi.ac.uk/pdbsum/5e38 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5e38 ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== Function == | == Function == | ||
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__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Myctu]] | |||
[[Category: Uracil phosphoribosyltransferase]] | [[Category: Uracil phosphoribosyltransferase]] | ||
[[Category: Bifani, P]] | [[Category: Bifani, P]] | ||
Revision as of 17:51, 16 November 2017
Structural basis of mapping the spontaneous mutations with 5-flourouracil in uracil phosphoribosyltransferase from Mycobacterium tuberculosisStructural basis of mapping the spontaneous mutations with 5-flourouracil in uracil phosphoribosyltransferase from Mycobacterium tuberculosis
Structural highlights
Function[UPP_MYCTU] Catalyzes the conversion of uracil and 5-phospho-alpha-D-ribose 1-diphosphate (PRPP) to UMP and diphosphate. Publication Abstract from PubMedTuberculosis (TB) remains the second leading cause of death from an infectious disease globally, despite the incessant efforts to control it. Research and development into new TB medicines is imperative for effective TB control; however, new strategies for the rational use of existing drugs, such as through the identification of new drug targets, could also significantly enhance this process. Key enzymes involved in the essential metabolic and regulatory pathways are usually sought in the pursuit of potential drug targets. Uracil phosphoribosyltransferase (UPRT) is a key salvage pathway enzyme in the synthesis of uridine 5'-monophosphate (UMP) and a probable target of 5-fluorouracil (5-FU) in Mycobacterium tuberculosis (Mtb). To date, there is no structure available for UPRT from Mtb (MtUPRT) that would assist in the identification of appropriate inhibitors for the enzyme. Here we report the structure of MtUPRT along with its spontaneous mutational studies in the presence of 5-FU. We further mapped these four single nucleotide polymorphisms (SNPs) onto the MtUPRT structure, with two residues found to be conserved among the MtUPRT homologs. Notably, none of these SNPs are located in the 5-FU binding pocket. However, the mutants harboring these mutations showed increased MICs (minimum inhibitory concentration) as compared to wild type strains. The present study will aid in the screening of inhibitors of MtUPRT and thus assist in TB drug design and development. Structural basis of mapping the spontaneous mutations with 5-flurouracil in uracil phosphoribosyltransferase from Mycobacterium tuberculosis.,Ghode P, Jobichen C, Ramachandran S, Bifani P, Sivaraman J Biochem Biophys Res Commun. 2015 Nov 20;467(3):577-82. doi:, 10.1016/j.bbrc.2015.09.133. Epub 2015 Oct 8. PMID:26456658[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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