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Grafting a new metal ligand in the cocatalytic site of B. cereus metallo‐β‐lactamase: Structural flexibility without loss of activity
Author(s) -
Rasia Rodolfo M.,
Ceolín Marcelo,
Vila Alejandro J.
Publication year - 2003
Publication title -
protein science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.353
H-Index - 175
eISSN - 1469-896X
pISSN - 0961-8368
DOI - 10.1110/ps.0301603
Subject(s) - active site , bacillus cereus , hydrolase , stereochemistry , enzyme , chemistry , cereus , ligand (biochemistry) , biochemistry , biology , bacteria , genetics , receptor
Metallo‐β‐lactamases are zinc enzymes able to hydrolyze the four‐membered ring of β‐lactam antibiotics, representing one of the latest generations of β‐lactamases. These enzymes belong to the zinc metallo‐hydrolase family of the β‐lactamase fold. Enzymes belonging to this family have a bimetallic active site whose structure varies among different members by point substitutions of the metal ligands. In this work, we have grafted new metal ligands into the metal binding site of BcII from Bacillus cereus that mimic the ligands present in other members of this superfamily. We have characterized spectroscopically and modeled the structure of the redesigned sites, which differ substantially from the wild‐type enzyme. Despite the changes introduced in the active site, the mutant enzymes retain almost full activity. These results shed some light on the possible evolutionary origin of these metalloenzymes.