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* Residue conservation analysis
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Gene Ontology (GO) functional annotation
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Biological process
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biosynthetic process
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1 term
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Biochemical function
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transferase activity
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1 term
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DOI no:
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Chem Biol
13:1143-1152
(2006)
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PubMed id:
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Insights into the synthesis of lipopolysaccharide and antibiotics through the structures of two retaining glycosyltransferases from family GT4.
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C.Martinez-Fleites,
M.Proctor,
S.Roberts,
D.N.Bolam,
H.J.Gilbert,
G.J.Davies.
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ABSTRACT
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Glycosyltransferases (GTs) catalyze the synthesis of the myriad glycoconjugates
that are central to life. One of the largest families is GT4, which contains
several enzymes of therapeutic significance, exemplified by WaaG and AviGT4.
WaaG catalyses a key step in lipopolysaccharide synthesis, while AviGT4,
produced by Streptomyces viridochromogenes, contributes to the synthesis of the
antibiotic avilamycin A. Here we present the crystal structure of both WaaG and
AviGT4. The two enzymes contain two "Rossmann-like" (beta/alpha/beta)
domains characteristic of the GT-B fold. Both recognition of the donor substrate
and the catalytic machinery is similar to other retaining GTs that display the
GT-B fold. Structural information is discussed with respect to the evolution of
GTs and the therapeutic significance of the two enzymes.
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Selected figure(s)
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Figure 1.
Figure 1. The Catalytic Action of Two Family GT4 GTs (A)
Schematic diagram of E. coli LPS. GlcN, D-glucosamine; Hep,
L-glycero-D-manno-heptose; P, phosphate; EtNP, 2-aminoethyl
phosphate; Glc, D-glucose; Gal, D-galactose. WaaG is responsible
for the addition of the first glucose moiety via an α-1,3
glycosidic linkage to Hep II. (B) Structure of the
antibiotic avilamycin A. Disruption of the avigt4 gene results
in a product lacking the eurekanate moiety (boxed) normally
bonded to the L-lyxose residue [8].
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Figure 5.
Figure 5. Electrostatic Surface Figures of WaaG and AviGT4
Surface representation of (A) WaaG and (B) AviGT4
colored by electrostatic potential (red, −3kT; blue +3kT,
where k is the Boltzmann constant and T is temperature),
calculated by the Adaptive Poisson-Boltzmann Solver (APBS)
program [44] and visualized with Pymol (DeLano Scientific LLC,
http://pymol.sourceforge.net/); ligands are shown in licorice
representation.
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The above figures are
reprinted
by permission from Cell Press:
Chem Biol
(2006,
13,
1143-1152)
copyright 2006.
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Figures were
selected
by an automated process.
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Literature references that cite this PDB file's key reference
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PubMed id
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Reference
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C.Luley-Goedl,
and
B.Nidetzky
(2010).
Carbohydrate synthesis by disaccharide phosphorylases: reactions, catalytic mechanisms and application in the glycosciences.
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Biotechnol J, 5,
1324-1338.
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S.F.Hansen,
E.Bettler,
A.Rinnan,
S.B.Engelsen,
and
C.Breton
(2010).
Exploring genomes for glycosyltransferases.
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Mol Biosyst, 6,
1773-1781.
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S.M.Batt,
T.Jabeen,
A.K.Mishra,
N.Veerapen,
K.Krumbach,
L.Eggeling,
G.S.Besra,
and
K.Fütterer
(2010).
Acceptor substrate discrimination in phosphatidyl-myo-inositol mannoside synthesis: structural and mutational analysis of mannosyltransferase Corynebacterium glutamicum PimB'.
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J Biol Chem, 285,
37741-37752.
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PDB codes:
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A.Ramos,
C.Olano,
A.F.Braña,
C.Méndez,
and
J.A.Salas
(2009).
Modulation of deoxysugar transfer by the elloramycin glycosyltransferase ElmGT through site-directed mutagenesis.
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J Bacteriol, 191,
2871-2875.
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D.Kaur,
M.E.Guerin,
H.Skovierová,
P.J.Brennan,
and
M.Jackson
(2009).
Chapter 2: Biogenesis of the cell wall and other glycoconjugates of Mycobacterium tuberculosis.
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Adv Appl Microbiol, 69,
23-78.
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F.Fan,
M.W.Vetting,
P.A.Frantom,
and
J.S.Blanchard
(2009).
Structures and mechanisms of the mycothiol biosynthetic enzymes.
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Curr Opin Chem Biol, 13,
451-459.
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F.Sheng,
X.Jia,
A.Yep,
J.Preiss,
and
J.H.Geiger
(2009).
The crystal structures of the open and catalytically competent closed conformation of Escherichia coli glycogen synthase.
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J Biol Chem, 284,
17796-17807.
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PDB codes:
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H.Claus,
K.Stummeyer,
J.Batzilla,
M.Mühlenhoff,
and
U.Vogel
(2009).
Amino acid 310 determines the donor substrate specificity of serogroup W-135 and Y capsule polymerases of Neisseria meningitidis.
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Mol Microbiol, 71,
960-971.
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H.M.Eriksson,
P.Wessman,
C.Ge,
K.Edwards,
and
A.Wieslander
(2009).
Massive formation of intracellular membrane vesicles in Escherichia coli by a monotopic membrane-bound lipid glycosyltransferase.
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J Biol Chem, 284,
33904-33914.
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M.E.Guerin,
D.Kaur,
B.S.Somashekar,
S.Gibbs,
P.Gest,
D.Chatterjee,
P.J.Brennan,
and
M.Jackson
(2009).
New insights into the early steps of phosphatidylinositol mannoside biosynthesis in mycobacteria: PimB' is an essential enzyme of Mycobacterium smegmatis.
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J Biol Chem, 284,
25687-25696.
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B.Henrissat,
G.Sulzenbacher,
and
Y.Bourne
(2008).
Glycosyltransferases, glycoside hydrolases: surprise, surprise!
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Curr Opin Struct Biol, 18,
527-533.
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C.Goedl,
and
B.Nidetzky
(2008).
The phosphate site of trehalose phosphorylase from Schizophyllum commune probed by site-directed mutagenesis and chemical rescue studies.
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FEBS J, 275,
903-913.
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C.J.Thibodeaux,
C.E.Melançon,
and
H.W.Liu
(2008).
Natural-product sugar biosynthesis and enzymatic glycodiversification.
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Angew Chem Int Ed Engl, 47,
9814-9859.
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G.J.Williams,
R.W.Gantt,
and
J.S.Thorson
(2008).
The impact of enzyme engineering upon natural product glycodiversification.
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Curr Opin Chem Biol, 12,
556-564.
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K.M.Ruane,
G.J.Davies,
and
C.Martinez-Fleites
(2008).
Crystal structure of a family GT4 glycosyltransferase from Bacillus anthracis ORF BA1558.
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Proteins, 73,
784-787.
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PDB code:
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K.Steiner,
A.Wojciechowska,
C.Schäffer,
and
J.H.Naismith
(2008).
Purification, crystallization and preliminary crystallographic analysis of WsaF, an essential rhamnosyltransferase from Geobacillus stearothermophilus.
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Acta Crystallogr Sect F Struct Biol Cryst Commun, 64,
1163-1165.
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K.Yokoyama,
Y.Yamamoto,
F.Kudo,
and
T.Eguchi
(2008).
Involvement of two distinct N-acetylglucosaminyltransferases and a dual-function deacetylase in neomycin biosynthesis.
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Chembiochem, 9,
865-869.
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L.L.Lairson,
B.Henrissat,
G.J.Davies,
and
S.G.Withers
(2008).
Glycosyltransferases: structures, functions, and mechanisms.
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Annu Rev Biochem, 77,
521-555.
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M.Barreras,
S.R.Salinas,
P.L.Abdian,
M.A.Kampel,
and
L.Ielpi
(2008).
Structure and Mechanism of GumK, a Membrane-associated Glucuronosyltransferase.
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J Biol Chem, 283,
25027-25035.
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PDB codes:
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M.W.Vetting,
P.A.Frantom,
and
J.S.Blanchard
(2008).
Structural and enzymatic analysis of MshA from Corynebacterium glutamicum: substrate-assisted catalysis.
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J Biol Chem, 283,
15834-15844.
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PDB codes:
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Y.Li,
Y.Chen,
X.Huang,
M.Zhou,
R.Wu,
S.Dong,
D.G.Pritchard,
P.Fives-Taylor,
and
H.Wu
(2008).
A conserved domain of previously unknown function in Gap1 mediates protein-protein interaction and is required for biogenesis of a serine-rich streptococcal adhesin.
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Mol Microbiol, 70,
1094-1104.
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Z.Fulton,
A.McAlister,
M.C.Wilce,
R.Brammananth,
L.Zaker-Tabrizi,
M.A.Perugini,
S.P.Bottomley,
R.L.Coppel,
P.K.Crellin,
J.Rossjohn,
and
T.Beddoe
(2008).
Crystal Structure of a UDP-glucose-specific Glycosyltransferase from a Mycobacterium Species.
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J Biol Chem, 283,
27881-27890.
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PDB codes:
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M.E.Guerin,
J.Kordulakova,
F.Schaeffer,
Z.Svetlikova,
A.Buschiazzo,
D.Giganti,
B.Gicquel,
K.Mikusova,
M.Jackson,
and
P.M.Alzari
(2007).
Molecular recognition and interfacial catalysis by the essential phosphatidylinositol mannosyltransferase PimA from mycobacteria.
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J Biol Chem, 282,
20705-20714.
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PDB codes:
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M.L.Klement,
L.Ojemyr,
K.E.Tagscherer,
G.Widmalm,
and
A.Wieslander
(2007).
A processive lipid glycosyltransferase in the small human pathogen Mycoplasma pneumoniae: involvement in host immune response.
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Mol Microbiol, 65,
1444-1457.
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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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