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[摘要]：Catalysis by S-adenosylmethionine synthetase has been investigated by quantum mechanical/molecular mechanical calculations, exploiting structures of the active Crystalline enzyme. The transition state energy of +19.1 kcal/mol computed For a nucleophilic attack of the methionyl sulfur on carbon-5' of the nucleotide was indistinguishable from the experimental (solution) value when the QM residues were an uncharged histidine that hydrogen bonds to the leaving oxygen-5' and an aspartate that chelates a Mg2+ ion, and was similar (+18.8 kcal/mol) when the QM region also included the active site arginine and lysines. The Computed energy difference between reactant and product was also consistent with their equimolar abundance in co-crystals. The calculated geometrical changes Support catalysis of a S(N)2 reaction through hydrogen bonding of the liberated oxygen-5' to the histidine, charge neutralization by the two Mg2+ ions, and stabilization of the product sulfonium cation through a close, non-bonded, contact between the sulfur and the ribose oxygen-4'. (C) 2009 Elsevier Inc. All rights reserved. |
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