Theoretical Study Of Catalytic Mechanism For DMSP Cleavage By RlDddP

Dimethylsulfide(DMS)released from the decomposition of dimethylsulphoniopropionate(DMSP)is the most abundant natural source of organic sulfides.RlDddP is a binuclear iron DMSP lyase capable of catalyzing the DMSP decomposition to DMS and acrylate.In this paper,using unrestricted density functional theory(UDFT)with the B3LYP functional,we have investigated the decomposition mechanism of dimethylsulphoniopropionate(DMSP)catalyzed by a DMSP lyase from Ruegeria lacuscaerulensis ITI₁157(RlDddP).We present the energetics for the RlDddP reaction and the characterization of the intermediates and transition states(TS)involved.(1)The RlDddP-catalyzed DMSP decomposition employs a concerted?-elimination mechanism,where the substrate?-proton abstraction by the Asp377 is coupled with the C?-S bond dissociation and C?=C?double bond formation.(2)It is demonstrated that the RlDddP reaction proceeds without any O?species bridging the two ferric ions,although an O?bridging species was observed in the crystal structures of RlDddP-inhibitor complexes.The presence of an O?bridging hydroxide or water will increase reaction barriers considerably.(3)It is found that a neutral Lys419 is more favorable for the RlDddP reaction than a protonated Lys419.The RlDddP enzyme is able to considerably decrease the Lys419 pK_a to a quite low value of 6.19 from common?10.5 to keep a high concentration of neural Lys419,consequently facilliting the catalysis.