View source for 4bqh


==Crystal structure of the uridine diphosphate N-acetylglucosamine pyrophosphorylase from Trypanosoma brucei in complex with inhibitor==
<StructureSection load='4bqh' size='340' side='right'caption='[[4bqh]], [[Resolution|resolution]] 1.75&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4bqh]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Trypanosoma_brucei Trypanosoma brucei]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4BQH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4BQH 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]] 1.75&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=9VU:(3S)-3-[2-(1,3-BENZODIOXOL-5-YL)-2-OXIDANYLIDENE-ETHYL]-4-BROMANYL-5-METHYL-3-OXIDANYL-1H-INDOL-2-ONE'>9VU</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=4bqh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4bqh OCA], [https://pdbe.org/4bqh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4bqh RCSB], [https://www.ebi.ac.uk/pdbsum/4bqh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4bqh ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/Q386Q8_TRYB2 Q386Q8_TRYB2] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Uridine diphosphate N-acetylglucosamine pyrophosphorylase (UAP) catalyses the final reaction in the biosynthesis of UDP-GlcNAc, an essential metabolite in many organisms including Trypanosoma brucei, the etiological agent of Human African Trypanosomiasis. High throughput screening of recombinant T. brucei UAP identified a UTP-competitive inhibitor with selectivity over the human counterpart despite the high level of conservation of active site residues. Biophysical characterisation of the UAP enzyme kinetics revealed that the human and trypanosome enzymes both display a strictly ordered bi-bi mechanism, but with the order of substrate binding reversed. Structural characterisation of the T. brucei UAP - inhibitor complex revealed that the inhibitor binds at an allosteric site absent in the human homologue that prevents the conformational rearrangement required to bind UTP. The identification of a selective inhibitory allosteric binding site in the parasite enzyme has therapeutic potential.

A novel allosteric inhibitor of the uridine diphosphate N-acetylglucosamine pyrophosphorylase from Trypanosoma brucei.,Urbaniak MD, Collie IT, Fang W, Aristotelous T, Eskilsson S, Raimi OG, Harrison J, Hopkins Navratolova I, Frearson JA, van Aalten DM, Ferguson MA ACS Chem Biol. 2013 Jul 8. PMID:23834437<ref>PMID:23834437</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4bqh" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Trypanosoma brucei]]
[[Category: Fang W]]
[[Category: Raimi OG]]
[[Category: VanAalten DMF]]