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| | <StructureSection load='3gf4' size='340' side='right'caption='[[3gf4]], [[Resolution|resolution]] 2.45Å' scene=''> | | <StructureSection load='3gf4' size='340' side='right'caption='[[3gf4]], [[Resolution|resolution]] 2.45Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3gf4]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/"bacillus_pneumoniae"_(schroeter_1886)_flugge_1886 "bacillus pneumoniae" (schroeter 1886) flugge 1886]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3GF4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3GF4 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3gf4]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Klebsiella_pneumoniae Klebsiella pneumoniae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3GF4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3GF4 FirstGlance]. <br> |
| - | </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=U5P:URIDINE-5-MONOPHOSPHATE'>U5P</scene>, <scene name='pdbligand=UPG:URIDINE-5-DIPHOSPHATE-GLUCOSE'>UPG</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.45Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1i8t|1i8t]], [[2bi7|2bi7]], [[2bi8|2bi8]], [[1wam|1wam]], [[1v0j|1v0j]]</div></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=U5P:URIDINE-5-MONOPHOSPHATE'>U5P</scene>, <scene name='pdbligand=UPG:URIDINE-5-DIPHOSPHATE-GLUCOSE'>UPG</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">glf, rfbD ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=573 "Bacillus pneumoniae" (Schroeter 1886) Flugge 1886])</td></tr> | + | |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/UDP-galactopyranose_mutase UDP-galactopyranose mutase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=5.4.99.9 5.4.99.9] </span></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=3gf4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3gf4 OCA], [https://pdbe.org/3gf4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3gf4 RCSB], [https://www.ebi.ac.uk/pdbsum/3gf4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3gf4 ProSAT]</span></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=3gf4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3gf4 OCA], [https://pdbe.org/3gf4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3gf4 RCSB], [https://www.ebi.ac.uk/pdbsum/3gf4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3gf4 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/GLF1_KLEPN GLF1_KLEPN]] Involved in the biosynthesis of the galactose-containing O-side-chain polysaccharide backbone structure of D-galactan I which is a key component of lipopolysaccharide (LPS). Catalyzes the interconversion through a 2-keto intermediate of uridine diphosphogalactopyranose (UDP-GalP) into uridine diphosphogalactofuranose (UDP-GalF) which is the biosynthetic precursor of galactofuranosyl residues.<ref>PMID:9020123</ref>
| + | [https://www.uniprot.org/uniprot/GLF1_KLEPN GLF1_KLEPN] Involved in the biosynthesis of the galactose-containing O-side-chain polysaccharide backbone structure of D-galactan I which is a key component of lipopolysaccharide (LPS). Catalyzes the interconversion through a 2-keto intermediate of uridine diphosphogalactopyranose (UDP-GalP) into uridine diphosphogalactofuranose (UDP-GalF) which is the biosynthetic precursor of galactofuranosyl residues.<ref>PMID:9020123</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| | + | [[Category: Klebsiella pneumoniae]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: UDP-galactopyranose mutase]]
| + | [[Category: Borrok MJ]] |
| - | [[Category: Borrok, M J]] | + | [[Category: Forest KT]] |
| - | [[Category: Forest, K T]] | + | [[Category: Gruber TD]] |
| - | [[Category: Gruber, T D]] | + | [[Category: Kiessling LL]] |
| - | [[Category: Kiessling, L L]] | + | |
| - | [[Category: Carbohydrate biosynthesis]]
| + | |
| - | [[Category: Fad]]
| + | |
| - | [[Category: Flavoenzyme]]
| + | |
| - | [[Category: Flavoprotein]]
| + | |
| - | [[Category: Isomerase]]
| + | |
| - | [[Category: Lipopolysaccharide biosynthesis]]
| + | |
| - | [[Category: Protein-ligand complex]]
| + | |
| Structural highlights
Function
GLF1_KLEPN Involved in the biosynthesis of the galactose-containing O-side-chain polysaccharide backbone structure of D-galactan I which is a key component of lipopolysaccharide (LPS). Catalyzes the interconversion through a 2-keto intermediate of uridine diphosphogalactopyranose (UDP-GalP) into uridine diphosphogalactofuranose (UDP-GalF) which is the biosynthetic precursor of galactofuranosyl residues.[1]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Galactofuranose (Galf) residues are present in cell wall glycoconjugates of numerous pathogenic microbes. Uridine 5'-diphosphate (UDP) Galf, the biosynthetic precursor of Galf-containing glycoconjugates, is produced from UDP-galactopyranose (UDP-Galp) by the flavoenzyme UDP-galactopyranose mutase (UGM). The gene encoding UGM (glf) is essential for the viability of pathogens, including Mycobacterium tuberculosis, and this finding underscores the need to understand how UGM functions. Considerable effort has been devoted to elucidating the catalytic mechanism of UGM, but progress has been hindered by a lack of structural data for an enzyme-substrate complex. Such data could reveal not only substrate binding interactions but how UGM can act preferentially on two very different substrates, UDP-Galp and UDP-Galf, yet avoid other structurally related UDP sugars present in the cell. Herein, we describe the first structure of a UGM-ligand complex, which provides insight into the catalytic mechanism and molecular basis for substrate selectivity. The structure of UGM from Klebsiella pneumoniae bound to the substrate analog UDP-glucose (UDP-Glc) was solved by X-ray crystallographic methods and refined to 2.5 A resolution. The ligand is proximal to the cofactor, a finding that is consistent with a proposed mechanism in which the reduced flavin engages in covalent catalysis. Despite this proximity, the glucose ring of the substrate analog is positioned such that it disfavors covalent catalysis. This orientation is consistent with data indicating that UDP-Glc is not a substrate for UGM. The relative binding orientations of UDP-Galp and UDP-Glc were compared using saturation transfer difference NMR. The results indicate that the uridine moiety occupies a similar location in both ligand complexes, and this relevant binding mode is defined by our structural data. In contrast, the orientations of the glucose and galactose sugar moieties differ. To understand the consequences of these differences, we derived a model for the productive UGM-substrate complex that highlights interactions that can contribute to catalysis and substrate discrimination.
Ligand binding and substrate discrimination by UDP-galactopyranose mutase.,Gruber TD, Borrok MJ, Westler WM, Forest KT, Kiessling LL J Mol Biol. 2009 Aug 14;391(2):327-40. Epub 2009 Jun 3. PMID:19500588[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Koplin R, Brisson JR, Whitfield C. UDP-galactofuranose precursor required for formation of the lipopolysaccharide O antigen of Klebsiella pneumoniae serotype O1 is synthesized by the product of the rfbDKPO1 gene. J Biol Chem. 1997 Feb 14;272(7):4121-8. PMID:9020123
- ↑ Gruber TD, Borrok MJ, Westler WM, Forest KT, Kiessling LL. Ligand binding and substrate discrimination by UDP-galactopyranose mutase. J Mol Biol. 2009 Aug 14;391(2):327-40. Epub 2009 Jun 3. PMID:19500588 doi:10.1016/j.jmb.2009.05.081
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