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PDBsum entry 1pmt
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References listed in PDB file
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Key reference
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Title
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A mixed disulfide bond in bacterial glutathione transferase: functional and evolutionary implications.
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Authors
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J.Rossjohn,
G.Polekhina,
S.C.Feil,
N.Allocati,
M.Masulli,
C.De illio,
M.W.Parker.
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Ref.
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Structure, 1998,
6,
721-734.
[DOI no: ]
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PubMed id
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Abstract
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BACKGROUND: Glutathione S-transferases (GSTs) are a multifunctional group of
enzymes, widely distributed in aerobic organisms, that have a critical role in
the cellular detoxification process. Unlike their mammalian counterparts,
bacterial GSTs often catalyze quite specific reactions, suggesting that their
roles in bacteria might be different. The GST from Proteus mirabilis (PmGST
B1-1) is known to bind certain antibiotics tightly and reduce the antimicrobial
activity of beta-lactam drugs. Hence, bacterial GSTs may play a part in
bacterial resistance towards antibiotics and are the subject of intense
interest. RESULTS: Here we present the structure of a bacterial GST, PmGST B1-1,
which has been determined from two different crystal forms. The enzyme adopts
the canonical GST fold although it shares less than 20% sequence identity with
GSTs from higher organisms. The most surprising aspect of the structure is the
observation that the substrate, glutathione, is covalently bound to Cys 10 of
the enzyme. In addition, the highly structurally conserved N-terminal domain is
found to have an additional beta strand. CONCLUSIONS: The crystal structure of
PmGST B1-1 has highlighted the importance of a cysteine residue in the catalytic
cycle. Sequence analyses suggest that a number of other GSTs share this
property, leading us to propose a new class of GSTs - the beta class. The data
suggest that the in vivo role of the beta class GSTs could be as metabolic or
redox enzymes rather than conjugating enzymes. Compelling evidence is presented
that the theta class of GSTs evolved from an ancestral member of the thioredoxin
superfamily.
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Figure 6.
Figure 6. Evolution of GSH thiol interactions within the
active sites of different GSTs. The active sites of GSTs from
three classes are shown: (a) bacterial theta class GST (b)
insect theta class GST [13]; and (c) human pi class GST [31].
GSH and residues involved in the interactions are shown in
ball-and-stick form. (The figure was produced using MOLSCRIPT
[56] and is adapted from Figure 5 of [12] © 1997 American
Chemical Society with kind permission of Richard Armstrong.)
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The above figure is
reprinted
by permission from Cell Press:
Structure
(1998,
6,
721-734)
copyright 1998.
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