Open AccessThe structure of Toho1 β‐lactamase in complex with penicillin reveals the role of Tyr105 in substrate recognition
Author(s) -
Langan Patricia S.,
Vandavasi Venu Gopal,
Weiss Kevin L.,
Cooper Jonathan B.,
Ginell Stephan L.,
Coates Leighton
Publication year - 2016
Publication title -
febs open bio
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.718
H-Index - 31
ISSN - 2211-5463
DOI - 10.1002/2211-5463.12132
Subject(s) - penicillin , substrate (aquarium) , chemistry , microbiology and biotechnology , stereochemistry , biology , antibiotics , ecology
The role of the conserved residue Tyr105 in class A β‐lactamases has been the subject of investigation using both structural studies and saturation mutagenesis. Both have shown that while it does not need to be strictly conserved for activity, it is important for substrate recognition. With this in mind we determined the crystal structure of Toho1 β‐lactamase at 15 K to 1.10 Å resolution in complex with penicillin. As expected a ring‐opened penicillin molecule bound to Ser70 the catalytic nucleophile, can clearly be seen in electron density in the active site. In addition to the trapped penicillin, however, are two additional intact ring‐closed penicillin molecules, captured by the enzyme through noncovalent interactions at the edge of the active site.