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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:
 [1];  [1];  [1];  [2];  [3];  [1]
  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
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Biological and Environmental Research (BER)
OSTI Identifier:
1331023
Alternate Identifier(s):
OSTI ID: 1331025; OSTI ID: 1623459
Grant/Contract Number:  
AC02-06CH11357
Resource Type:
Published Article
Journal Name:
FEBS Open Bio
Additional Journal Information:
Journal Name: FEBS Open Bio Journal Volume: 6 Journal Issue: 12; Journal ID: ISSN 2211-5463
Publisher:
Wiley Blackwell (John Wiley & Sons)
Country of Publication:
Country unknown/Code not available
Language:
English
Subject:
Biochemistry & Molecular Biology; antibiotic resistance; antibiotics; enzyme; enzyme structure; X-ray crystallograph

Citation Formats

Langan, Patricia S., Vandavasi, Venu Gopal, Weiss, Kevin L., Cooper, Jonathan B., Ginell, Stephan L., and Coates, Leighton. The structure of Toho1 β-lactamase in complex with penicillin reveals the role of Tyr105 in substrate recognition. Country unknown/Code not available: N. p., 2016. Web. doi:10.1002/2211-5463.12132.
Langan, Patricia S., Vandavasi, Venu Gopal, Weiss, Kevin L., Cooper, Jonathan B., Ginell, Stephan L., & Coates, Leighton. The structure of Toho1 β-lactamase in complex with penicillin reveals the role of Tyr105 in substrate recognition. Country unknown/Code not available. doi:10.1002/2211-5463.12132.
Langan, Patricia S., Vandavasi, Venu Gopal, Weiss, Kevin L., Cooper, Jonathan B., Ginell, Stephan L., and Coates, Leighton. Mon . "The structure of Toho1 β-lactamase in complex with penicillin reveals the role of Tyr105 in substrate recognition". Country unknown/Code not available. doi:10.1002/2211-5463.12132.
@article{osti_1331023,
title = {The structure of Toho1 β-lactamase in complex with penicillin reveals the role of Tyr105 in substrate recognition},
author = {Langan, Patricia S. and Vandavasi, Venu Gopal and Weiss, Kevin L. and Cooper, Jonathan B. and Ginell, Stephan L. and Coates, Leighton},
abstractNote = {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.},
doi = {10.1002/2211-5463.12132},
journal = {FEBS Open Bio},
number = 12,
volume = 6,
place = {Country unknown/Code not available},
year = {2016},
month = {11}
}

Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record
DOI: 10.1002/2211-5463.12132

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Cited by: 1 work
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    Works referencing / citing this record:

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