View source for 5eqf


==Crystal structure of oxidized UDP-galactopyranose mutase from Corynebacterium diphtheriae with UDP bound in closed form==
<StructureSection load='5eqf' size='340' side='right'caption='[[5eqf]], [[Resolution|resolution]] 2.15&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5eqf]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Corynebacterium_diphtheriae_NCTC_13129 Corynebacterium diphtheriae NCTC 13129]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5EQF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5EQF 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]] 2.145&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=UDP:URIDINE-5-DIPHOSPHATE'>UDP</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=5eqf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5eqf OCA], [https://pdbe.org/5eqf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5eqf RCSB], [https://www.ebi.ac.uk/pdbsum/5eqf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5eqf ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/Q6NER4_CORDI Q6NER4_CORDI] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
UDP-galactopyranose mutase (Glf or UGM) catalyzes the formation of uridine 5'-diphosphate-alpha-d-galactofuranose (UDP-Galf) from UDP-galactopyranose (UDP-Galp). The enzyme is required for the production of Galf-containing glycans. UGM is absent in mammals, but members of the Corynebacterineae suborder require UGM for cell envelope biosynthesis. The need for UGM in some pathogens has prompted the search for inhibitors that could serve as antibiotic leads. Optimizing inhibitor potency, however, has been challenging. The UGM from Klebsiella pneumoniae (KpUGM), which is not required for viability, is more effectively impeded by small-molecule inhibitors than are essential UGMs from species such as Mycobacterium tuberculosis or Corynebacterium diphtheriae. Why KpUGM is more susceptible to inhibition than other orthologs is not clear. One potential source of difference is UGM ortholog conformation. We previously determined a structure of CdUGM bound to a triazolothiadiazine inhibitor in the open form, but it was unclear whether the small-molecule inhibitor bound this form or to the closed form. By varying the terminal tag (CdUGM-His6 and GSG-CdUGM), we crystallized CdUGM to capture the enzyme in different conformations. These structures reveal a pocket in the active site that can be exploited to augment inhibitor affinity. Moreover, they suggest the inhibitor binds the open form of most prokaryotic UGMs but can bind the closed form of KpUGM. This model and the structures suggest strategies for optimizing inhibitor potency by exploiting UGM conformational flexibility.

Conformational Control of UDP-Galactopyranose Mutase Inhibition.,Wangkanont K, Winton VJ, Forest KT, Kiessling LL Biochemistry. 2017 Aug 1;56(30):3983-3992. doi: 10.1021/acs.biochem.7b00189. Epub, 2017 Jul 20. PMID:28608671<ref>PMID:28608671</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5eqf" style="background-color:#fffaf0;"></div>

==See Also==
*[[UDP-galactopyranose mutase 3D structures|UDP-galactopyranose mutase 3D structures]]
== References ==
<references/>
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</StructureSection>
[[Category: Corynebacterium diphtheriae NCTC 13129]]
[[Category: Large Structures]]
[[Category: Forest KT]]
[[Category: Kiessling LL]]
[[Category: Wangkanont K]]