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The 3‐D structure of a zinc metallo‐beta‐lactamase from Bacillus cereus reveals a new type of protein fold.
Author(s) -
Carfi A.,
Pares S.,
Duée E.,
Galleni M.,
Duez C.,
Frère J. M.,
Dideberg O.
Publication year - 1995
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1002/j.1460-2075.1995.tb00174.x
Subject(s) - biology , bacillus cereus , cereus , fold (higher order function) , zinc , microbiology and biotechnology , bacterial protein , bacteria , genetics , mechanical engineering , materials science , engineering , metallurgy
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.