A QM/MM Study of the Catalytic Mechanism of Imidazolonepropionase from Bacillus subtilis

【作者】 盛翔； 刘永军；

【机构】 山东大学理论化学研究所；

【摘要】 Imidazolonepropionase(Hut I)is the third enzyme in histidine degradation pathway,which catalyzes the conversion of 4-imidazolone-5-propionic acid(IPA)to N-formimino-L-glutamic acid(FGA).In this work,the catalytic mechanism of Hut I has been studied by using QM/MM approach.Our calculation results indicate that the catalytic reaction starts from the proton transfer(from residue E252 to IPA)followed by the formation of a covalent bond between Zn-binding hydroxyl and IPA to generate a tetrahedral intermediate,which then collapses to give the final product FGA.The ligation of hydroxyl with IPA is the rate-limiting step with an energy barrier of 18.7 kcal/mol.During the reaction,residues H185 and S329 and a residue cluster that consists of R89,E92,Y102and Y152 play important roles in stabilizing substrate IPA by forming hydrogen bonds directly or via water molecules.Our results may provide useful information for the regulation of enzyme activity and development of related biocatalytic applications更多还原

【Abstract】 Imidazolonepropionase(Hut I)is the third enzyme in histidine degradation pathway,which catalyzes the conversion of 4-imidazolone-5-propionic acid(IPA)to N-formimino-L-glutamic acid(FGA).In this work,the catalytic mechanism of Hut I has been studied by using QM/MM approach.Our calculation results indicate that the catalytic reaction starts from the proton transfer(from residue E252 to IPA)followed by the formation of a covalent bond between Zn-binding hydroxyl and IPA to generate a tetrahedral intermediate,which then collapses to give the final product FGA.The ligation of hydroxyl with IPA is the rate-limiting step with an energy barrier of 18.7 kcal/mol.During the reaction,residues H185 and S329 and a residue cluster that consists of R89,E92,Y102and Y152 play important roles in stabilizing substrate IPA by forming hydrogen bonds directly or via water molecules.Our results may provide useful information for the regulation of enzyme activity and development of related biocatalytic applications更多还原