Dal Peraro Matteo, Vila Alejandro J, Carloni Paolo
International School for Advanced Studies, SISSA and INFM-DEMOCRITOS, Trieste, Italy.
Proteins. 2004 Feb 15;54(3):412-23. doi: 10.1002/prot.10554.
Structure and dynamics of substrate binding (cefotaxime) to the catalytic pocket of the mononuclear zinc-beta-lactamase from Bacillus cereus are investigated by molecular dynamics simulations. The calculations, which are based on the hydrogen-bond pattern recently proposed by Dal Peraro et al. (J Biol Inorg Chem 2002; 7:704-712), are carried out for both the free and the complexed enzyme. In the resting state, active site pattern and temperature B-factors are in agreement with crystallographic data. In the complexed form, cefotaxime is accommodated into a stable orientation in the catalytic pocket within the nanosecond timescale, interacting with the enzyme zinc-bound hydroxide and the surrounding loops. The beta-lactam ring remains stable and very close to the hydroxide nucleophile agent, giving a stable representation of the productive enzyme-substrate complex.
通过分子动力学模拟研究了底物（头孢噻肟）与蜡样芽孢杆菌单核锌β-内酰胺酶催化口袋的结合结构和动力学。这些计算基于Dal Peraro等人最近提出的氢键模式（《生物无机化学杂志》2002年；7:704 - 712），对游离酶和复合酶都进行了计算。在静止状态下，活性位点模式和温度B因子与晶体学数据一致。在复合形式中，头孢噻肟在纳秒时间尺度内以稳定的取向容纳在催化口袋中，与酶结合锌的氢氧化物和周围的环相互作用。β-内酰胺环保持稳定且非常接近氢氧化物亲核试剂，给出了生产性酶-底物复合物的稳定表征。
