Insights into trehalose synthesis provided by the structure of the retaining glucosyltransferase OtsA

R P  Gibson; J P  Turkenburg; S J  Charnock; R  Lloyd; G J  Davies

Insights into trehalose synthesis provided by the structure of the retaining glucosyltransferase OtsA

R P Gibson, J P Turkenburg, S J Charnock, R Lloyd, G J Davies

Chemistry

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

Abstract

Trehalose is a nonreducing disaccharide that plays a major role in many organisms, most notably in survival and stress responses. In Mycobacterium tuberculosis, it plays a central role as the carbohydrate core of numerous immunogenic glycolipids including "cord factor" (trehalose 6,6'-dimycolate). The classical pathway for trehalose synthesis involves the condensation of UDP-glucose and glucose-6-phosphate to afford trehalose-6-phosphate, catalyzed by the retaining glycosyltransferase OtsA. The configurations of two anomeric positions are set simultaneously, resulting in the formation of a double glycoside. The three-dimensional structure of the Escherichia coli OtsA, in complex with both UDP and glucose-6-phosphate, reveals the active site at the interface of two beta/alpha/beta domains. The overall structure and the intimate details of the catalytic machinery reveal a striking similarity to glycogen phosphorylase, indicating a strong evolutionary link and suggesting a common catalytic mechanism.

Original language	English
Pages (from-to)	1337-1346
Number of pages	10
Journal	Chemistry & Biology
Volume	9
Issue number	12
Publication status	Published - Dec 2002

Keywords

CARBOHYDRATE-ACTIVE ENZYMES
CRYSTAL-STRUCTURE
GLYCOGEN-PHOSPHORYLASE
SACCHAROMYCES-CEREVISIAE
BLOOD-GROUP
CELL-WALL
BIOSYNTHESIS
SUBSTRATE
SYNTHASE
COMPLEX

Cite this

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title = "Insights into trehalose synthesis provided by the structure of the retaining glucosyltransferase OtsA",

abstract = "Trehalose is a nonreducing disaccharide that plays a major role in many organisms, most notably in survival and stress responses. In Mycobacterium tuberculosis, it plays a central role as the carbohydrate core of numerous immunogenic glycolipids including {"}cord factor{"} (trehalose 6,6'-dimycolate). The classical pathway for trehalose synthesis involves the condensation of UDP-glucose and glucose-6-phosphate to afford trehalose-6-phosphate, catalyzed by the retaining glycosyltransferase OtsA. The configurations of two anomeric positions are set simultaneously, resulting in the formation of a double glycoside. The three-dimensional structure of the Escherichia coli OtsA, in complex with both UDP and glucose-6-phosphate, reveals the active site at the interface of two beta/alpha/beta domains. The overall structure and the intimate details of the catalytic machinery reveal a striking similarity to glycogen phosphorylase, indicating a strong evolutionary link and suggesting a common catalytic mechanism.",

keywords = "CARBOHYDRATE-ACTIVE ENZYMES, CRYSTAL-STRUCTURE, GLYCOGEN-PHOSPHORYLASE, SACCHAROMYCES-CEREVISIAE, BLOOD-GROUP, CELL-WALL, BIOSYNTHESIS, SUBSTRATE, SYNTHASE, COMPLEX",

author = "Gibson, {R P} and Turkenburg, {J P} and Charnock, {S J} and R Lloyd and Davies, {G J}",

year = "2002",

month = dec,

language = "English",

volume = "9",

pages = "1337--1346",

journal = "Chemistry & Biology",

issn = "1074-5521",

publisher = "Elsevier",

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TY - JOUR

T1 - Insights into trehalose synthesis provided by the structure of the retaining glucosyltransferase OtsA

AU - Gibson, R P

AU - Turkenburg, J P

AU - Charnock, S J

AU - Lloyd, R

AU - Davies, G J

PY - 2002/12

Y1 - 2002/12

N2 - Trehalose is a nonreducing disaccharide that plays a major role in many organisms, most notably in survival and stress responses. In Mycobacterium tuberculosis, it plays a central role as the carbohydrate core of numerous immunogenic glycolipids including "cord factor" (trehalose 6,6'-dimycolate). The classical pathway for trehalose synthesis involves the condensation of UDP-glucose and glucose-6-phosphate to afford trehalose-6-phosphate, catalyzed by the retaining glycosyltransferase OtsA. The configurations of two anomeric positions are set simultaneously, resulting in the formation of a double glycoside. The three-dimensional structure of the Escherichia coli OtsA, in complex with both UDP and glucose-6-phosphate, reveals the active site at the interface of two beta/alpha/beta domains. The overall structure and the intimate details of the catalytic machinery reveal a striking similarity to glycogen phosphorylase, indicating a strong evolutionary link and suggesting a common catalytic mechanism.

AB - Trehalose is a nonreducing disaccharide that plays a major role in many organisms, most notably in survival and stress responses. In Mycobacterium tuberculosis, it plays a central role as the carbohydrate core of numerous immunogenic glycolipids including "cord factor" (trehalose 6,6'-dimycolate). The classical pathway for trehalose synthesis involves the condensation of UDP-glucose and glucose-6-phosphate to afford trehalose-6-phosphate, catalyzed by the retaining glycosyltransferase OtsA. The configurations of two anomeric positions are set simultaneously, resulting in the formation of a double glycoside. The three-dimensional structure of the Escherichia coli OtsA, in complex with both UDP and glucose-6-phosphate, reveals the active site at the interface of two beta/alpha/beta domains. The overall structure and the intimate details of the catalytic machinery reveal a striking similarity to glycogen phosphorylase, indicating a strong evolutionary link and suggesting a common catalytic mechanism.

KW - CARBOHYDRATE-ACTIVE ENZYMES

KW - CRYSTAL-STRUCTURE

KW - GLYCOGEN-PHOSPHORYLASE

KW - SACCHAROMYCES-CEREVISIAE

KW - BLOOD-GROUP

KW - CELL-WALL

KW - BIOSYNTHESIS

KW - SUBSTRATE

KW - SYNTHASE

KW - COMPLEX

M3 - Article

SN - 1074-5521

VL - 9

SP - 1337

EP - 1346

JO - Chemistry & Biology

JF - Chemistry & Biology

IS - 12

ER -