Jump to main content
Jump to site search

Issue 47, 2013
Previous Article Next Article

Penicillin's catalytic mechanism revealed by inelastic neutrons and quantum chemical theory

Author affiliations

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).

Graphical abstract: Penicillin's catalytic mechanism revealed by inelastic neutrons and quantum chemical theory

Back to tab navigation

Supplementary files

Publication details

The article was received on 27 Feb 2013, accepted on 28 May 2013 and first published on 12 Jun 2013


Article type: Paper
DOI: 10.1039/C3CP50868D
Phys. Chem. Chem. Phys., 2013,15, 20447-20455

  •   Request permissions

    Penicillin's catalytic mechanism revealed by inelastic neutrons and quantum chemical theory

    Z. Mucsi, G. A. Chass, P. Ábrányi-Balogh, B. Jójárt, D. Fang, A. J. Ramirez-Cuesta, B. Viskolcz and I. G. Csizmadia, Phys. Chem. Chem. Phys., 2013, 15, 20447
    DOI: 10.1039/C3CP50868D

Search articles by author

Spotlight

Advertisements