The structure of Toho1 β‐lactamase in complex with penicillin reveals the role of Tyr105 in substrate recognition
- Biology and Soft Matter Division Oak Ridge National Laboratory TN USA
- Birkbeck University of London UK
- Structural Biology Center Argonne National Laboratory IL USA
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.
- Research Organization:
- Argonne National Laboratory (ANL), Argonne, IL (United States)
- Sponsoring Organization:
- USDOE Office of Science (SC)
- Grant/Contract Number:
- AC02-06CH11357
- OSTI ID:
- 1331023
- Alternate ID(s):
- OSTI ID: 1331025; OSTI ID: 1623459
- Journal Information:
- FEBS Open Bio, Journal Name: FEBS Open Bio Vol. 6 Journal Issue: 12; ISSN 2211-5463
- Publisher:
- Wiley Blackwell (John Wiley & Sons)Copyright Statement
- Country of Publication:
- Netherlands
- Language:
- English
Web of Science
Similar Records
A close look onto structural models and primary ligands of metallo-β-lactamases
Mapping the determinants of catalysis and substrate specificity of the antibiotic resistance enzyme CTX-M β-lactamase