The structure of Toho1 β-lactamase in complex with penicillin reveals the role of Tyr105 in substrate recognition

Patricia S. Langan, Venu Gopal Vandavasi, Kevin L. Weiss, Jonathan B. Cooper, Stephan L. Ginell, Leighton Coates

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

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.

Original languageEnglish
Pages (from-to)1170-1177
Number of pages8
JournalFEBS Open Bio
Volume6
Issue number12
DOIs
StatePublished - Dec 1 2016

Funding

This research was sponsored by the Laboratory Directed Research and Development Program at Oak Ridge National Laboratory, which is managed by UT-Battelle, LLC, for the U.S. Department of Energy (DOE). Research at ORNL's Spallation Neutron Source was sponsored by the Scientific User Facilities Division, Office of Basic Energy Sciences, U.S. Department of Energy. The Office of Biological and Environmental Research supported research at Oak Ridge National Laboratory's Center for Structural Molecular Biology (CSMB), using facilities supported by the Scientific User Facilities Division, Office of Basic Energy Sciences, U.S. Department of Energy. Results shown in this report are derived from work performed at Argonne National Laboratory (ANL), Structural Biology Center at the Advanced Photon Source. ANL is operated by UChicago Argonne, LLC, for the U.S. Department of Energy, Office of Biological and Environmental Research under contract DE-AC02-06CH11357.

Keywords

  • X-ray crystallography
  • antibiotic resistance
  • antibiotics
  • enzyme
  • enzyme structure

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