View source for 4rph


==Crystal structure of Micobacterium tuberculosis UDP-Galactopyranose mutase in complex with substrate UDP-Galp (reduced)==
<StructureSection load='4rph' size='340' side='right'caption='[[4rph]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4rph]] is a 3 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=4RPH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4RPH 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]] 2.6&#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=GDU:GALACTOSE-URIDINE-5-DIPHOSPHATE'>GDU</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=4rph FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4rph OCA], [https://pdbe.org/4rph PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4rph RCSB], [https://www.ebi.ac.uk/pdbsum/4rph PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4rph ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/GLF_MYCTU GLF_MYCTU] Catalyzes the interconversion through a 2-keto intermediate of uridine diphosphogalactopyranose (UDP-GalP) into uridine diphosphogalactofuranose (UDP-GalF) which is a key building block for cell wall construction in Mycobacterium tuberculosis.<ref>PMID:9692181</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
UDP-Galactopyranose mutase (UGM) is a flavin-containing enzyme that catalyzes the reversible conversion of UDP-galactopyranose (UDP-Galp) to UDP-galactofuranose (UDP-Galf) and plays a key role in the biosynthesis of the mycobacterial cell wall galactofuran. A soluble, active form of UGM from Mycobacterium tuberculosis (MtUGM) was obtained from a dual His6-MBP-tagged MtUGM construct. We present the first complex structures of MtUGM with bound substrate UDP-Galp (both oxidized flavin and reduced flavin). In addition, we have determined the complex structures of MtUGM with inhibitors (UDP and the dideoxy-tetrafluorinated analogues of both UDP-Galp (UDP-F4-Galp) and UDP-Galf (UDP-F4-Galf)), which represent the first complex structures of UGM with an analogue in the furanose form, as well as the first structures of dideoxy-tetrafluorinated sugar analogues bound to a protein. These structures provide detailed insight into ligand recognition by MtUGM and show an overall binding mode similar to those reported for other prokaryotic UGMs. The binding of the ligand induces conformational changes in the enzyme, allowing ligand binding and active-site closure. In addition, the complex structure of MtUGM with UDP-F4-Galf reveals the first detailed insight into how the furanose moiety binds to UGM. In particular, this study confirmed that the furanoside adopts a high-energy conformation (4E) within the catalytic pocket. Moreover, these investigations provide structural insights into the enhanced binding of the dideoxy-tetrafluorinated sugars compared to unmodified analogues. These results will help in the design of carbohydrate mimetics and drug development, and show the enormous possibilities for the use of polyfluorination in the design of carbohydrate mimetics.

Structural Basis of Ligand Binding to UDP-Galactopyranose Mutase from Mycobacterium tuberculosis Using Substrate and Tetrafluorinated Substrate Analogues.,van Straaten KE, Kuttiyatveetil JR, Sevrain CM, Villaume SA, Jimenez-Barbero J, Linclau B, Vincent SP, Sanders DA J Am Chem Soc. 2015 Jan 16. PMID:25562380<ref>PMID:25562380</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4rph" style="background-color:#fffaf0;"></div>

==See Also==
*[[UDP-galactopyranose mutase 3D structures|UDP-galactopyranose mutase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Mycobacterium tuberculosis H37Rv]]
[[Category: Sanders DAR]]
[[Category: Van Straaten KE]]