View source for 3mj4


==Crystal structure of UDP-galactopyranose mutase in complex with phosphonate analog of UDP-galactopyranose==
<StructureSection load='3mj4' size='340' side='right'caption='[[3mj4]], [[Resolution|resolution]] 2.65&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3mj4]] is a 10 chain structure with sequence from [https://en.wikipedia.org/wiki/Deinococcus_radiodurans_R1 Deinococcus radiodurans R1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3MJ4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3MJ4 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]] 2.65&#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=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=UDP:URIDINE-5-DIPHOSPHATE'>UDP</scene>, <scene name='pdbligand=URM:(((2S,3R,4S,5R,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)methyl)phosphonic+(((2R,3S,4R,5R)-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-3,4-dihydroxytetrahydrofuran-2-yl)methyl+phosphoric)+anhydride'>URM</scene>, <scene name='pdbligand=XYL:D-XYLITOL'>XYL</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=3mj4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3mj4 OCA], [https://pdbe.org/3mj4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3mj4 RCSB], [https://www.ebi.ac.uk/pdbsum/3mj4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3mj4 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/Q9RYF1_DEIRA Q9RYF1_DEIRA] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
UDP (uridine diphosphate) galactopyranose mutase (UGM) is involved in the cell wall biosynthesis of many pathogenic microorganisms. UGM catalyzes the reversible conversion of UDP-alpha-d-galactopyranose into UDP-alpha-d-galactofuranose, with the latter being the precursor of galactofuranose (Galf) residues in cell walls. Glycoconjugates of Galf are essential components in the cell wall of various pathogenic bacteria, including Mycobacterium tuberculosis, the causative agent of tuberculosis. The absence of Galf in humans and its bacterial requirement make UGM a potential target for developing novel antibacterial agents. In this article, we report the synthesis, inhibitory activity, and X-ray crystallographic studies of UDP-phosphono-galactopyranose, a nonhydrolyzable C-glycosidic phosphonate. This is the first report on the synthesis of a phosphonate analog of UDP-alpha-d-galactopyranose by a chemoenzymatic phosphoryl coupling method. The phosphonate was evaluated against three bacterial UGMs and showed only moderate inhibition. We determined the crystal structure of the phosphonate analog bound to Deinococcus radiodurans UGM at 2.6 A resolution. The phosphonate analog is bound in a novel conformation not observed in UGM-substrate complex structures or in other enzyme-sugar nucleotide phosphonate complexes. This complex structure provides a structural basis for the observed micromolar inhibition towards UGM. Steric clashes, loss of electrostatic stabilization between an active-site arginine (Arg305) and the phosphonate analog, and a 180 degrees flip of the hexose moiety account for the differences in the binding orientations of the isosteric phosphonate analog and the physiological substrate. This provides new insight into the ability of a sugar-nucleotide-binding enzyme to orient a substrate analog in an unexpected geometry and should be taken into consideration in designing such enzyme inhibitors.

Chemoenzymatic Synthesis, Inhibition Studies, and X-ray Crystallographic Analysis of the Phosphono Analog of UDP-Galp as an Inhibitor and Mechanistic Probe for UDP-Galactopyranose Mutase.,Partha SK, Sadeghi-Khomami A, Slowski K, Kotake T, Thomas NR, Jakeman DL, Sanders DA J Mol Biol. 2010 Nov 5;403(4):578-90. Epub 2010 Sep 17. PMID:20850454<ref>PMID:20850454</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 3mj4" style="background-color:#fffaf0;"></div>

==See Also==
*[[UDP-galactopyranose mutase 3D structures|UDP-galactopyranose mutase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Deinococcus radiodurans R1]]
[[Category: Large Structures]]
[[Category: Jakeman DL]]
[[Category: Karunan Partha S]]
[[Category: Kotake T]]
[[Category: Sadeghi-Khomami A]]
[[Category: Sanders DAR]]
[[Category: Slowski K]]
[[Category: Thomas NR]]