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PDBsum entry 1udc
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Isomerase PDB id
1udc

 

 

 

 

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Contents
Protein chain
338 a.a. *
Ligands
NAD
UFM
PGE
EDO ×3
Metals
_NA ×3
Waters ×559
* Residue conservation analysis
PDB id:
1udc
Name: Isomerase
Title: Structure of udp-galactose-4-epimerase complexed with udp-mannose
Structure: Udp-galactose-4-epimerase. Chain: a. Synonym: epimerase. Ec: 5.1.3.2
Source: Escherichia coli. Organism_taxid: 562
Biol. unit: Homo-Dimer (from PDB file)
Resolution:
1.65Å     R-factor:   0.177    
Authors: J.B.Thoden,H.M.Holden
Key ref:
J.B.Thoden et al. (1997). Structural analysis of UDP-sugar binding to UDP-galactose 4-epimerase from Escherichia coli. Biochemistry, 36, 6294-6304. PubMed id: 9174344 DOI: 10.1021/bi970025j
Date:
06-Jan-97     Release date:   14-Jan-98    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P09147  (GALE_ECOLI) -  UDP-glucose 4-epimerase from Escherichia coli (strain K12)
Seq:
Struc: 		338 a.a.
338 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.5.1.3.2  - UDP-glucose 4-epimerase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

      Pathway: 		UDP-glucose, UDP-galactose and UDP-glucuronate Biosynthesis
      Reaction: UDP-alpha-D-glucose = UDP-alpha-D-galactose
UDP-alpha-D-glucose
Bound ligand (Het Group name = UFM)
corresponds exactly 		= UDP-alpha-D-galactose
      Cofactor: NAD(+)
NAD(+)
Bound ligand (Het Group name = NAD) corresponds exactly
Molecule diagrams generated from .mol files obtained from the KEGG ftp site

 

 
    Added reference    
 
 
DOI no: 10.1021/bi970025j Biochemistry 36:6294-6304 (1997)
PubMed id: 9174344  
 
 
Structural analysis of UDP-sugar binding to UDP-galactose 4-epimerase from Escherichia coli.
J.B.Thoden, A.D.Hegeman, G.Wesenberg, M.C.Chapeau, P.A.Frey, H.M.Holden.
 
  ABSTRACT  
 
UDP-galactose 4-epimerase from Escherichia coli catalyzes the interconversion of UDP-galactose and UDP-glucose through the transient reduction of the tightly bound cofactor NAD+. The enzyme is unique among the NAD+-dependent enzymes in that it promotes stereospecific reduction of the cofactor but nonstereospecific hydride return during normal catalysis. In addition to hydride transfer, the reaction mechanism of epimerase involves two key features: the abstraction of a proton from the 4'-hydroxyl group of glucose or galactose by an active site base and the rotation of a 4-ketopyranose intermediate in the active site pocket. To address the second issue of movement within the active site, the X-ray structures of reduced epimerase complexed with UDP-mannose, UDP-4-deoxy-4-fluoro-alpha-D-galactose, or UDP-4-deoxy-4-fluoro-alpha-D-glucose have been determined and refined to 1.65, 1.8, and 1.65 A resolution, respectively. A comparison of these models to that of the previously determined epimerase/NADH/UDP-glucose abortive complex reveals that the active site accommodates the various sugars by simple rearrangements of water molecules rather than by large changes in side chain conformations. In fact, the polypeptide chains for all of the epimerase/NADH/UDP-sugar complexes studied thus far are remarkably similar and can be superimposed with root-mean-square deviations of not greater than 0.24 A. The only significant differences between the various enzyme/UDP-sugar models occur in two of the dihedral angles defining the conformation of the UDP-sugar ligands.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21117131 C.Dalvit, and A.Vulpetti (2011).
Fluorine-protein interactions and ¹⁹F NMR isotropic chemical shifts: An empirical correlation with implications for drug design.
  ChemMedChem, 6, 104-114.  
20717852 H.J.Kim, S.Y.Kang, J.J.Park, and P.Kim (2011).
Novel Activity of UDP-Galactose-4-Epimerase for Free Monosaccharide and Activity Improvement by Active Site-Saturation Mutagenesis.
  Appl Biochem Biotechnol, 163, 444-451.  
19644687 P.Schweiger, and U.Deppenmeier (2010).
Analysis of aldehyde reductases from Gluconobacter oxydans 621H.
  Appl Microbiol Biotechnol, 85, 1025-1031.  
20506248 T.Kowatz, J.P.Morrison, M.E.Tanner, and J.H.Naismith (2010).
The crystal structure of the Y140F mutant of ADP-L-glycero-D-manno-heptose 6-epimerase bound to ADP-beta-D-mannose suggests a one base mechanism.
  Protein Sci, 19, 1337-1343.
PDB codes: 2x6t 2x86
19168656 K.A.Kazimierczak, K.P.Scott, D.Kelly, and R.I.Aminov (2009).
Tetracycline resistome of the organic pig gut.
  Appl Environ Microbiol, 75, 1717-1722.  
19421452 R.M.Mizanur, and N.L.Pohl (2009).
Phosphomannose isomerase/GDP-mannose pyrophosphorylase from Pyrococcus furiosus: a thermostable biocatalyst for the synthesis of guanidinediphosphate-activated and mannose-containing sugar nucleotides.
  Org Biomol Chem, 7, 2135-2139.  
18188677 J.S.Chhay, C.A.Vargas, T.J.McCorvie, J.L.Fridovich-Keil, and D.J.Timson (2008).
Analysis of UDP-galactose 4'-epimerase mutations associated with the intermediate form of type III galactosaemia.
  J Inherit Metab Dis, 31, 108-116.  
19011750 K.L.Kavanagh, H.Jörnvall, B.Persson, and U.Oppermann (2008).
Medium- and short-chain dehydrogenase/reductase gene and protein families : the SDR superfamily: functional and structural diversity within a family of metabolic and regulatory enzymes.
  Cell Mol Life Sci, 65, 3895-3906.  
18570380 R.Banerjee, M.W.Pennington, A.Garza, and I.S.Owens (2008).
Mapping the UDP-glucuronic acid binding site in UDP-glucuronosyltransferase-1A10 by homology-based modeling: confirmation with biochemical evidence.
  Biochemistry, 47, 7385-7392.  
17912370 G.V.Louie, T.J.Baiga, M.E.Bowman, T.Koeduka, J.H.Taylor, S.M.Spassova, E.Pichersky, and J.P.Noel (2007).
Structure and reaction mechanism of basil eugenol synthase.
  PLoS ONE, 2, e993.
PDB codes: 2qw8 2qx7 2qys 2qzz 2r2g 2r6j
17138581 J.Maple, and S.G.Møller (2007).
Plastid division: evolution, mechanism and complexity.
  Ann Bot, 99, 565-579.  
16936924 J.H.Naismith (2006).
Inferring the chemical mechanism from structures of enzymes.
  Chem Soc Rev, 35, 763-770.  
16539386 J.Yu, and R.P.Mason (2006).
Synthesis and characterization of novel lacZ gene reporter molecules: detection of beta-galactosidase activity by 19F nuclear magnetic resonance of polyglycosylated fluorinated vitamin B6.
  J Med Chem, 49, 1991-1999.  
  16946458 M.S.Alphey, A.Burton, M.D.Urbaniak, G.J.Boons, M.A.Ferguson, and W.N.Hunter (2006).
Trypanosoma brucei UDP-galactose-4'-epimerase in ternary complex with NAD+ and the substrate analogue UDP-4-deoxy-4-fluoro-alpha-D-galactose.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 62, 829-834.
PDB code: 2cnb
16302980 D.J.Timson (2005).
Functional analysis of disease-causing mutations in human UDP-galactose 4-epimerase.
  FEBS J, 272, 6170-6177.  
15480888 D.L.Waters, T.A.Holton, E.M.Ablett, L.S.Lee, and R.J.Henry (2005).
cDNA microarray analysis of developing grape (Vitis vinifera cv. Shiraz) berry skin.
  Funct Integr Genomics, 5, 40-58.  
16133308 D.Terefe, and T.Tatlioglu (2005).
Isolation of a partial sequence of a putative nucleotide sugar epimerase, which may involve in stamen development in cucumber (Cucumis sativus L.).
  Theor Appl Genet, 111, 1300-1307.  
15809294 G.J.Williams, S.D.Breazeale, C.R.Raetz, and J.H.Naismith (2005).
Structure and function of both domains of ArnA, a dual function decarboxylase and a formyltransferase, involved in 4-amino-4-deoxy-L-arabinose biosynthesis.
  J Biol Chem, 280, 23000-23008.
PDB codes: 2bll 2bln
15939024 P.Z.Gatzeva-Topalova, A.P.May, and M.C.Sousa (2005).
Structure and mechanism of ArnA: conformational change implies ordered dehydrogenase mechanism in key enzyme for polymyxin resistance.
  Structure, 13, 929-942.
PDB codes: 1z73 1z74 1z75 1z7b 1z7e
14739333 N.A.Webb, A.M.Mulichak, J.S.Lam, H.L.Rocchetta, and R.M.Garavito (2004).
Crystal structure of a tetrameric GDP-D-mannose 4,6-dehydratase from a bacterial GDP-D-rhamnose biosynthetic pathway.
  Protein Sci, 13, 529-539.
PDB code: 1rpn
15016816 N.Ishiyama, C.Creuzenet, J.S.Lam, and A.M.Berghuis (2004).
Crystal structure of WbpP, a genuine UDP-N-acetylglucosamine 4-epimerase from Pseudomonas aeruginosa: substrate specificity in udp-hexose 4-epimerases.
  J Biol Chem, 279, 22635-22642.
PDB codes: 1sb8 1sb9
15491143 P.Z.Gatzeva-Topalova, A.P.May, and M.C.Sousa (2004).
Crystal structure of Escherichia coli ArnA (PmrI) decarboxylase domain. A key enzyme for lipid A modification with 4-amino-4-deoxy-L-arabinose and polymyxin resistance.
  Biochemistry, 43, 13370-13379.
PDB code: 1u9j
12969423 M.Mølhøj, R.Verma, and W.D.Reiter (2003).
The biosynthesis of the branched-chain sugar d-apiose in plants: functional cloning and characterization of a UDP-d-apiose/UDP-d-xylose synthase from Arabidopsis.
  Plant J, 35, 693-703.  
13129921 T.Min, H.Kasahara, D.L.Bedgar, B.Youn, P.K.Lawrence, D.R.Gang, S.C.Halls, H.Park, J.L.Hilsenbeck, L.B.Davin, N.G.Lewis, C.Kang, and N.G.Lewis (2003).
Crystal structures of pinoresinol-lariciresinol and phenylcoumaran benzylic ether reductases and their relationship to isoflavone reductases.
  J Biol Chem, 278, 50714-50723.
PDB codes: 1qyc 1qyd
12361482 A.J.Edgar (2002).
The human L-threonine 3-dehydrogenase gene is an expressed pseudogene.
  BMC Genet, 3, 18.  
12192068 C.A.Bottoms, P.E.Smith, and J.J.Tanner (2002).
A structurally conserved water molecule in Rossmann dinucleotide-binding domains.
  Protein Sci, 11, 2125-2137.  
12057956 C.K.Raymond, E.H.Sims, A.Kas, D.H.Spencer, T.V.Kutyavin, R.G.Ivey, Y.Zhou, R.Kaul, J.B.Clendenning, and M.V.Olson (2002).
Genetic variation at the O-antigen biosynthetic locus in Pseudomonas aeruginosa.
  J Bacteriol, 184, 3614-3622.  
12019271 J.B.Thoden, J.M.Henderson, J.L.Fridovich-Keil, and H.M.Holden (2002).
Structural analysis of the Y299C mutant of Escherichia coli UDP-galactose 4-epimerase. Teaching an old dog new tricks.
  J Biol Chem, 277, 27528-27534.
PDB codes: 1lrj 1lrk 1lrl
11877387 J.L.Moriarity, K.J.Hurt, A.C.Resnick, P.B.Storm, W.Laroy, R.L.Schnaar, and S.H.Snyder (2002).
UDP-glucuronate decarboxylase, a key enzyme in proteoglycan synthesis: cloning, characterization, and localization.
  J Biol Chem, 277, 16968-16975.  
11418766 B.Guillot, C.Lecomte, A.Cousson, C.Scherf, and C.Jelsch (2001).
High-resolution neutron structure of nicotinamide adenine dinucleotide.
  Acta Crystallogr D Biol Crystallogr, 57, 981-989.  
11580835 C.Creuzenet, and J.S.Lam (2001).
Topological and functional characterization of WbpM, an inner membrane UDP-GlcNAc C6 dehydratase essential for lipopolysaccharide biosynthesis in Pseudomonas aeruginosa.
  Mol Microbiol, 41, 1295-1310.  
11380265 E.Berger, A.Arabshahi, Y.Wei, J.F.Schilling, and P.A.Frey (2001).
Acid-base catalysis by UDP-galactose 4-epimerase: correlations of kinetically measured acid dissociation constants with thermodynamic values for tyrosine 149.
  Biochemistry, 40, 6699-6705.  
11208024 E.T.Johnson, S.Ryu, H.Yi, B.Shin, H.Cheong, and G.Choi (2001).
Alteration of a single amino acid changes the substrate specificity of dihydroflavonol 4-reductase.
  Plant J, 25, 325-333.  
11003139 M.D.Burkart, S.P.Vincent, A.Düffels, B.W.Murray, S.V.Ley, and C.H.Wong (2000).
Chemo-enzymatic synthesis of fluorinated sugar nucleotide: useful mechanistic probes for glycosyltransferases.
  Bioorg Med Chem, 8, 1937-1946.  
10089470 L.Ding, Y.Zhang, A.M.Deacon, S.E.Ealick, Y.Ni, P.Sun, and W.G.Coleman (1999).
Crystallization and preliminary X-ray diffraction studies of the lipopolysaccharide core biosynthetic enzyme ADP-L-glycero-D-mannoheptose 6-epimerase from Escherichia coli K-12.
  Acta Crystallogr D Biol Crystallogr, 55, 685-688.  
10455186 M.Graninger, B.Nidetzky, D.E.Heinrichs, C.Whitfield, and P.Messner (1999).
Characterization of dTDP-4-dehydrorhamnose 3,5-epimerase and dTDP-4-dehydrorhamnose reductase, required for dTDP-L-rhamnose biosynthesis in Salmonella enterica serovar Typhimurium LT2.
  J Biol Chem, 274, 25069-25077.  
10027985 R.Muñoz, R.López, M.de Frutos, and E.García (1999).
First molecular characterization of a uridine diphosphate galacturonate 4-epimerase: an enzyme required for capsular biosynthesis in Streptococcus pneumoniae type 1.
  Mol Microbiol, 31, 703-713.  
10480878 S.Menon, M.Stahl, R.Kumar, G.Y.Xu, and F.Sullivan (1999).
Stereochemical course and steady state mechanism of the reaction catalyzed by the GDP-fucose synthetase from Escherichia coli.
  J Biol Chem, 274, 26743-26750.  
9708982 J.B.Thoden, and H.M.Holden (1998).
Dramatic differences in the binding of UDP-galactose and UDP-glucose to UDP-galactose 4-epimerase from Escherichia coli.
  Biochemistry, 37, 11469-11477.
PDB codes: 1a9y 1a9z
9817848 M.Rizzi, M.Tonetti, P.Vigevani, L.Sturla, A.Bisso, A.D.Flora, D.Bordo, and M.Bolognesi (1998).
GDP-4-keto-6-deoxy-D-mannose epimerase/reductase from Escherichia coli, a key enzyme in the biosynthesis of GDP-L-fucose, displays the structural characteristics of the RED protein homology superfamily.
  Structure, 6, 1453-1465.
PDB code: 1bws
9862812 W.S.Somers, M.L.Stahl, and F.X.Sullivan (1998).
GDP-fucose synthetase from Escherichia coli: structure of a unique member of the short-chain dehydrogenase/reductase family that catalyzes two distinct reactions at the same active site.
  Structure, 6, 1601-1612.
PDB codes: 1bsv 1fxs 1gfs
9271498 Y.Liu, J.B.Thoden, J.Kim, E.Berger, A.M.Gulick, F.J.Ruzicka, H.M.Holden, and P.A.Frey (1997).
Mechanistic roles of tyrosine 149 and serine 124 in UDP-galactose 4-epimerase from Escherichia coli.
  Biochemistry, 36, 10675-10684.
PDB code: 1kvu
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.

 

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