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Persistent URL
http://purl.org/net/epubs/work/65737
Record Status
Checked
Record Id
65737
Title
Penicillin's catalytic mechanism revealed by inelastic neutrons and quantum chemical theory
Contributors
Z Mucsi (Toronto U.)
,
GA Chass (Queen Mary University of London)
,
P Ábrányi-Balogh (Szeged U.)
,
B Jójárt (Szeged U.)
,
D Fang (Beijing Normal U.)
,
AJ Ramirez-Cuesta (STFC Rutherford Appleton Lab.)
,
B Viskolcz (Szeged U.)
,
IG Csizmadia (Toronto U.)
Abstract
Penicillin, travels through bodily fluids, targeting and acylatively inactivating enzymes responsible for cell-wall synthesis in gram-positive bacteria. Somehow, it avoids metabolic degradation remaining inactive en route. To resolve this ability to switch from a non-active, to a highly reactive form, we investigated the dynamic structure-activity relationship of penicillin by inelastic neutron spectroscopy, reaction kinetics, NMR and multi-scale theoretical modelling (QM/MM and post-HF ab initio). Results show that by a self-activating physiological pH-dependent two-step proton-mediated process, penicillin changes geometry to activate its irreversibly reactive acylation, facilitated by systemic intramolecular energy management and cooperative vibrations. This dynamic mechanism is confirmed by the first ever reported characterisation of an antibiotic by neutrons, achieved on the TOSCA instrument (ISIS facility, RAL, UK).
Organisation
ISIS
,
ISIS-TOSCA
,
STFC
Keywords
Funding Information
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Language
English (EN)
Type
Details
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Year
Journal Article
Phys Chem Chem Phys
15 (2013): 20447-20455.
doi:10.1039/C3CP50868D
2013
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