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Linker modified novel bisubstrate analog inhibitors 4-7 for serotonin N-acetyltransferase (arylalkylamine N-acetyltransferase, AANAT) have been designed and synthesized. Examination of these inhibitors with AANAT in vitro suggested that: (i) linker hydrogen bonding makes only modest contributions to the affinity of bisubstrate analog inhibitors studied; (ii) greater than or equal to four methylene...
Transition state theory has provided no convincing explanation for the nearly universal observation of complexes of enzymes with substrates. Bimolecular catalytic reactions are assumed here to take place through reactive encounter complexes defined as the subset of reactant state species able to proceed directly to low lying energy levels at the transition state. By assessing the probability of these...
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