Serine protease acylation proceeds with a subtle re-orientation of the histidine ring at the tetrahedral intermediate.
نویسندگان
چکیده
The acylation mechanism of a prototypical serine protease trypsin and its complete free energy reaction profile have been determined by Born-Oppenheimer ab initio QM/MM molecular dynamics simulations with umbrella sampling.
منابع مشابه
Insights into the serine protease mechanism from atomic resolution structures of trypsin reaction intermediates.
Atomic resolution structures of trypsin acyl-enzymes and a tetrahedral intermediate analog, along with previously solved structures representing the Michaelis complex, are used to reconstruct events in the catalytic cycle of this classic serine protease. Structural comparisons provide insight into active site adjustments involved in catalysis. Subtle motions of the catalytic serine and histidin...
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The charge relay ststem and its role in the acylation of serine proteinases is studied using the partial retention of diatomic differential overlap (PRDDO) technique to perform approximate ab initio molecular orbital calculations on a model of the enzyme-substrate complex. The aspartate in the charge relay system is seen to act as the ultimate proton acceptor during the charging of the serine n...
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عنوان ژورنال:
- Chemical communications
دوره 47 5 شماره
صفحات -
تاریخ انتشار 2011