title: The structure of Toho1 β-lactamase in complex with penicillin reveals the role of Tyr105 in substrate recognition.
abstract: 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.
authors.affiliation: Biology and Soft Matter Division Oak Ridge National Laboratory TN USA.
authors.forename: Patricia S
authors.initials: PS
authors.lastname: Langan
authors.affiliation: Biology and Soft Matter Division Oak Ridge National Laboratory TN USA.
authors.forename: Venu Gopal
authors.initials: VG
authors.lastname: Vandavasi
authors.affiliation: Biology and Soft Matter Division Oak Ridge National Laboratory TN USA.
authors.forename: Kevin L
authors.initials: KL
authors.lastname: Weiss
authors.affiliation: Birkbeck University of London UK.
authors.forename: Jonathan B
authors.initials: JB
authors.lastname: Cooper
authors.affiliation: Structural Biology Center Argonne National Laboratory IL USA.
authors.forename: Stephan L
authors.initials: SL
authors.lastname: Ginell
authors.affiliation: Biology and Soft Matter Division Oak Ridge National Laboratory TN USA.
authors.forename: Leighton
authors.initials: L
authors.lastname: Coates
keywords: X‐ray crystallography; antibiotic resistance; antibiotics; enzyme; enzyme structure