期刊
PHYSICAL CHEMISTRY CHEMICAL PHYSICS
卷 15, 期 47, 页码 20447-20455出版社
ROYAL SOC CHEMISTRY
DOI: 10.1039/c3cp50868d
关键词
-
资金
- EPSRC, UK [EP/H030077/1, EP/H030077/2]
- Royal Society [IE120096]
- National Natural Science Foundation of China [21073016]
- Scientific Research Foundation of Beijing Normal University [2009SC-1]
- [TAMOP-4.2.2.A-11/1/KONV-2012-0047]
- [TAMOP-4.2.2.C-11/1/KONV-2012-0010]
- EPSRC [EP/H030077/1, EP/H030077/2] Funding Source: UKRI
- Engineering and Physical Sciences Research Council [EP/H030077/1, EP/H030077/2] Funding Source: researchfish
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).
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据