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Langan PS, Vandavasi VG, Weiss KL, et al. The structure of Toho1 β-lactamase in complex with penicillin reveals the role of Tyr105 in substrate recognition. FEBS Open Bio. 2016;6(12):1170-1177doi: 10.1002/2211-5463.12132.
Langan, P. S., Vandavasi, V. G., Weiss, K. L., Cooper, J. B., Ginell, S. L., & Coates, L. (2016). The structure of Toho1 β-lactamase in complex with penicillin reveals the role of Tyr105 in substrate recognition. FEBS open bio, 6(12), 1170-1177. https://doi.org/10.1002/2211-5463.12132
Langan, Patricia S, et al. "The structure of Toho1 β-lactamase in complex with penicillin reveals the role of Tyr105 in substrate recognition." FEBS open bio vol. 6,12 (2016): 1170-1177. doi: https://doi.org/10.1002/2211-5463.12132
Langan PS, Vandavasi VG, Weiss KL, Cooper JB, Ginell SL, Coates L. The structure of Toho1 β-lactamase in complex with penicillin reveals the role of Tyr105 in substrate recognition. FEBS Open Bio. 2016 Nov 07;6(12):1170-1177. doi: 10.1002/2211-5463.12132. eCollection 2016 Dec. PMID: 28255534; PMCID: PMC5324766.
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FEBS Open Bio. 2016 Nov 07;6(12):1170-1177. doi: 10.1002/2211-5463.12132. eCollection 2016 Dec.

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

FEBS open bio

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

Affiliations

  1. Biology and Soft Matter Division Oak Ridge National Laboratory TN USA.
  2. Birkbeck University of London UK.
  3. Structural Biology Center Argonne National Laboratory IL USA.

PMID: 28255534 PMCID: PMC5324766 DOI: 10.1002/2211-5463.12132

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.

Keywords: X‐ray crystallography; antibiotic resistance; antibiotics; enzyme; enzyme structure

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