Neutron and X-ray crystal structures of a perdeuterated enzyme inhibitor complex reveal the catalytic proton network of the Toho-1 β-lactamase for the acylation reaction

Stephen J. Tomanicek; Robert F. Standaert; Kevin L. Weiss; Andreas Ostermann; Tobias E. Schrader; Joseph D. Ng; Leighton Coates

doi:10.1074/jbc.M112.436238

Neutron and X-ray crystal structures of a perdeuterated enzyme inhibitor complex reveal the catalytic proton network of the Toho-1 β-lactamase for the acylation reaction

Stephen J. Tomanicek
, Robert F. Standaert
, Kevin L. Weiss
, Andreas Ostermann
, Tobias E. Schrader
, Joseph D. Ng
, Leighton Coates

Research output: Contribution to journal › Article › peer-review

39 Scopus citations

Abstract

Background: Antibiotic resistance from extended-spectrum β-lactamases (ESBLs) makes infections more dangerous and difficult to treat. Results: Neutron and x-ray crystal structures were determined for an ESBL in complex with an acylation transition state analog. Conclusion: Glu-166 is implicated as the general base in the acylation reaction. Significance: Understanding the catalytic mechanism of β-lactamases will lead to improved antibiotics and β-lactamase inhibitors.

Original language	English
Pages (from-to)	4715-4722
Number of pages	8
Journal	Journal of Biological Chemistry
Volume	288
Issue number	7
DOIs	https://doi.org/10.1074/jbc.M112.436238
State	Published - Feb 15 2013

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Tomanicek, S. J., Standaert, R. F., Weiss, K. L., Ostermann, A., Schrader, T. E., Ng, J. D., & Coates, L. (2013). Neutron and X-ray crystal structures of a perdeuterated enzyme inhibitor complex reveal the catalytic proton network of the Toho-1 β-lactamase for the acylation reaction. Journal of Biological Chemistry, 288(7), 4715-4722. https://doi.org/10.1074/jbc.M112.436238

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title = "Neutron and X-ray crystal structures of a perdeuterated enzyme inhibitor complex reveal the catalytic proton network of the Toho-1 β-lactamase for the acylation reaction",

abstract = "Background: Antibiotic resistance from extended-spectrum β-lactamases (ESBLs) makes infections more dangerous and difficult to treat. Results: Neutron and x-ray crystal structures were determined for an ESBL in complex with an acylation transition state analog. Conclusion: Glu-166 is implicated as the general base in the acylation reaction. Significance: Understanding the catalytic mechanism of β-lactamases will lead to improved antibiotics and β-lactamase inhibitors.",

author = "Tomanicek, \{Stephen J.\} and Standaert, \{Robert F.\} and Weiss, \{Kevin L.\} and Andreas Ostermann and Schrader, \{Tobias E.\} and Ng, \{Joseph D.\} and Leighton Coates",

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doi = "10.1074/jbc.M112.436238",

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Tomanicek, SJ, Standaert, RF, Weiss, KL, Ostermann, A, Schrader, TE, Ng, JD & Coates, L 2013, 'Neutron and X-ray crystal structures of a perdeuterated enzyme inhibitor complex reveal the catalytic proton network of the Toho-1 β-lactamase for the acylation reaction', Journal of Biological Chemistry, vol. 288, no. 7, pp. 4715-4722. https://doi.org/10.1074/jbc.M112.436238

Neutron and X-ray crystal structures of a perdeuterated enzyme inhibitor complex reveal the catalytic proton network of the Toho-1 β-lactamase for the acylation reaction. / Tomanicek, Stephen J.; Standaert, Robert F.; Weiss, Kevin L. et al.
In: Journal of Biological Chemistry, Vol. 288, No. 7, 15.02.2013, p. 4715-4722.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Neutron and X-ray crystal structures of a perdeuterated enzyme inhibitor complex reveal the catalytic proton network of the Toho-1 β-lactamase for the acylation reaction

AU - Tomanicek, Stephen J.

AU - Standaert, Robert F.

AU - Weiss, Kevin L.

AU - Ostermann, Andreas

AU - Schrader, Tobias E.

AU - Ng, Joseph D.

AU - Coates, Leighton

PY - 2013/2/15

Y1 - 2013/2/15

N2 - Background: Antibiotic resistance from extended-spectrum β-lactamases (ESBLs) makes infections more dangerous and difficult to treat. Results: Neutron and x-ray crystal structures were determined for an ESBL in complex with an acylation transition state analog. Conclusion: Glu-166 is implicated as the general base in the acylation reaction. Significance: Understanding the catalytic mechanism of β-lactamases will lead to improved antibiotics and β-lactamase inhibitors.

AB - Background: Antibiotic resistance from extended-spectrum β-lactamases (ESBLs) makes infections more dangerous and difficult to treat. Results: Neutron and x-ray crystal structures were determined for an ESBL in complex with an acylation transition state analog. Conclusion: Glu-166 is implicated as the general base in the acylation reaction. Significance: Understanding the catalytic mechanism of β-lactamases will lead to improved antibiotics and β-lactamase inhibitors.

UR - https://www.scopus.com/pages/publications/84874077280

U2 - 10.1074/jbc.M112.436238

DO - 10.1074/jbc.M112.436238

M3 - Article

C2 - 23255594

AN - SCOPUS:84874077280

SN - 0021-9258

VL - 288

SP - 4715

EP - 4722

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

IS - 7

ER -

Neutron and X-ray crystal structures of a perdeuterated enzyme inhibitor complex reveal the catalytic proton network of the Toho-1 β-lactamase for the acylation reaction

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