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Title
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The 3-D structure of a zinc metallo-beta-lactamase from Bacillus cereus reveals a new type of protein fold.
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Authors
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A.Carfi,
S.Pares,
E.Duée,
M.Galleni,
C.Duez,
J.M.Frère,
O.Dideberg.
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Ref.
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Embo J, 1995,
14,
4914-4921.
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PubMed id
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Abstract
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The 3-D structure of Bacillus cereus (569/H/9) beta-lactamase (EC 3.5.2.6),
which catalyses the hydrolysis of nearly all beta-lactams, has been solved at
2.5 A resolution by the multiple isomorphous replacement method, with density
modification and phase combination, from crystals of the native protein and of a
specially designed mutant (T97C). The current model includes 212 of the 227
amino acid residues, the zinc ion and 10 water molecules. The protein is folded
into a beta beta sandwich with helices on each external face. To our knowledge,
this fold has never been observed. An approximate internal molecular symmetry is
found, with a 2-fold axis passing roughly through the zinc ion and suggesting a
possible gene duplication. The active site is located at one edge of the beta
beta sandwich and near the N-terminal end of a helix. The zinc ion is
coordinated by three histidine residues (86, 88 and 149) and a water molecule. A
sequence comparison of the relevant metallo-beta-lactamases, based on this
protein structure, highlights a few well-conserved amino acid residues. The
structure shows that most of these residues are in the active site. Among these,
aspartic acid 90 and histidine 210 participate in a proposed catalytic mechanism
for beta-lactam hydrolysis.
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