Insights into the synthesis of lipopolysaccharide and antibiotics through the structures of two retaining glycosyltransferases from family GT4

Carlos Martinez-Fleites; Mark Proctor; Shirley Roberts; David N. Bolam; Harry J. Gilbert; Gideon J. Davies

doi:10.1016/j.chembiol.2006.09.005

Insights into the synthesis of lipopolysaccharide and antibiotics through the structures of two retaining glycosyltransferases from family GT4

Carlos Martinez-Fleites, Mark Proctor, Shirley Roberts, David N. Bolam, Harry J. Gilbert, Gideon J. Davies

Chemistry

Research output: Contribution to journal › Article › peer-review

Abstract

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.

Original language	English
Pages (from-to)	1143-1152
Number of pages	10
Journal	Chemistry & Biology
Volume	13
Issue number	11
DOIs	https://doi.org/10.1016/j.chembiol.2006.09.005
Publication status	Published - Nov 2006

Keywords

ESCHERICHIA-COLI
CRYSTAL-STRUCTURES
OLIGOSACCHARIDE SUBSTRATE
BETA-GLUCOSYLTRANSFERASE
GLYCOGEN-PHOSPHORYLASE
UDP-GLUCOSE
BIOSYNTHESIS
ALIGNMENT
SYNTHASE
ENZYMES

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10.1016/j.chembiol.2006.09.005

Cite this

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title = "Insights into the synthesis of lipopolysaccharide and antibiotics through the structures of two retaining glycosyltransferases from family GT4",

abstract = "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.",

keywords = "ESCHERICHIA-COLI, CRYSTAL-STRUCTURES, OLIGOSACCHARIDE SUBSTRATE, BETA-GLUCOSYLTRANSFERASE, GLYCOGEN-PHOSPHORYLASE, UDP-GLUCOSE, BIOSYNTHESIS, ALIGNMENT, SYNTHASE, ENZYMES",

author = "Carlos Martinez-Fleites and Mark Proctor and Shirley Roberts and Bolam, {David N.} and Gilbert, {Harry J.} and Davies, {Gideon J.}",

year = "2006",

month = nov,

doi = "10.1016/j.chembiol.2006.09.005",

language = "English",

volume = "13",

pages = "1143--1152",

journal = "Chemistry & Biology",

issn = "1074-5521",

publisher = "Elsevier",

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TY - JOUR

T1 - Insights into the synthesis of lipopolysaccharide and antibiotics through the structures of two retaining glycosyltransferases from family GT4

AU - Martinez-Fleites, Carlos

AU - Proctor, Mark

AU - Roberts, Shirley

AU - Bolam, David N.

AU - Gilbert, Harry J.

AU - Davies, Gideon J.

PY - 2006/11

Y1 - 2006/11

N2 - 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.

AB - 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.

KW - ESCHERICHIA-COLI

KW - CRYSTAL-STRUCTURES

KW - OLIGOSACCHARIDE SUBSTRATE

KW - BETA-GLUCOSYLTRANSFERASE

KW - GLYCOGEN-PHOSPHORYLASE

KW - UDP-GLUCOSE

KW - BIOSYNTHESIS

KW - ALIGNMENT

KW - SYNTHASE

KW - ENZYMES

U2 - 10.1016/j.chembiol.2006.09.005

DO - 10.1016/j.chembiol.2006.09.005

M3 - Article

SN - 1074-5521

VL - 13

SP - 1143

EP - 1152

JO - Chemistry & Biology

JF - Chemistry & Biology

IS - 11

ER -