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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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growth
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4 terms
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Biochemical function
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transferase activity, transferring hexosyl groups
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3 terms
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DOI no:
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Plos One
3:e3748
(2008)
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PubMed id:
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Mycobacterium tuberculosis glucosyl-3-phosphoglycerate synthase: structure of a key enzyme in methylglucose lipopolysaccharide biosynthesis.
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P.J.Pereira,
N.Empadinhas,
L.Albuquerque,
B.Sá-Moura,
M.S.da Costa,
S.Macedo-Ribeiro.
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ABSTRACT
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Tuberculosis constitutes today a serious threat to human health worldwide,
aggravated by the increasing number of identified multi-resistant strains of
Mycobacterium tuberculosis, its causative agent, as well as by the lack of
development of novel mycobactericidal compounds for the last few decades. The
increased resilience of this pathogen is due, to a great extent, to its complex,
polysaccharide-rich, and unusually impermeable cell wall. The synthesis of this
essential structure is still poorly understood despite the fact that enzymes
involved in glycosidic bond synthesis represent more than 1% of all M.
tuberculosis ORFs identified to date. One of them is GpgS, a retaining
glycosyltransferase (GT) with low sequence homology to any other GTs of known
structure, which has been identified in two species of mycobacteria and shown to
be essential for the survival of M. tuberculosis. To further understand the
biochemical properties of M. tuberculosis GpgS, we determined the
three-dimensional structure of the apo enzyme, as well as of its ternary complex
with UDP and 3-phosphoglycerate, by X-ray crystallography, to a resolution of
2.5 and 2.7 A, respectively. GpgS, the first enzyme from the newly established
GT-81 family to be structurally characterized, displays a dimeric architecture
with an overall fold similar to that of other GT-A-type glycosyltransferases.
These three-dimensional structures provide a molecular explanation for the
enzyme's preference for UDP-containing donor substrates, as well as for its
glucose versus mannose discrimination, and uncover the structural determinants
for acceptor substrate selectivity. Glycosyltransferases constitute a growing
family of enzymes for which structural and mechanistic data urges. The
three-dimensional structures of M. tuberculosis GpgS now determined provide such
data for a novel enzyme family, clearly establishing the molecular determinants
for substrate recognition and catalysis, while providing an experimental
scaffold for the structure-based rational design of specific inhibitors, which
lay the foundation for the development of novel anti-tuberculosis therapies.
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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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N.Empadinhas,
P.J.Pereira,
L.Albuquerque,
J.Costa,
B.Sá-Moura,
A.T.Marques,
S.Macedo-Ribeiro,
and
M.S.da Costa
(2011).
Functional and structural characterization of a novel mannosyl-3-phosphoglycerate synthase from Rubrobacter xylanophilus reveals its dual substrate specificity.
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Mol Microbiol, 79,
76-93.
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PDB codes:
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D.Kaur,
H.Pham,
G.Larrouy-Maumus,
M.Rivière,
V.Vissa,
M.E.Guerin,
G.Puzo,
P.J.Brennan,
and
M.Jackson
(2009).
Initiation of methylglucose lipopolysaccharide biosynthesis in mycobacteria.
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PLoS ONE, 4,
e5447.
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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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Links
