Williams J W, Northrop D B
J Antibiot (Tokyo). 1979 Nov;32(11):1147-54. doi: 10.7164/antibiotics.32.1147.
Gentamicin acetyltransferase I will catalyze acyl transfer from chloroacetylcoenzyme A to form 3-N-chloroacetylgentamicin. This product can be linked to coenzyme A to form a multisubstrate analog by nucleophilic displacement of the chlorine by the sulfur of coenzyme A. The analog can be purified by selective binding to cationic and anionic ion exchange resins. Kinetic analysis of a time-dependent onset and reversal of inhibition of gentamicin acetyltransferase I by the purified multisubstrate analog yields an inhibition constant of 5 approximately 20 x 10(-10) M. The inhibitor does not potentiate antibiotic activity against resistant Escherichia coli. Nevertheless, the effectiveness of the tight-binding between the enzyme and the multisubstrate analog demonstrates that inhibitors of resistance can be designed and prepared by specific enzymatic synthesis.
庆大霉素乙酰转移酶I将催化氯乙酰辅酶A的酰基转移，形成3-N-氯乙酰庆大霉素。该产物可通过辅酶A的硫对氯的亲核取代与辅酶A连接形成多底物类似物。该类似物可通过与阳离子和阴离子离子交换树脂的选择性结合进行纯化。对纯化的多底物类似物对庆大霉素乙酰转移酶I的抑制作用随时间的起始和逆转进行动力学分析，得出抑制常数约为5×10(-10)M至20×10(-10)M。该抑制剂不会增强对耐药性大肠杆菌的抗生素活性。然而，酶与多底物类似物之间紧密结合的有效性表明，可以通过特定的酶促合成来设计和制备耐药性抑制剂。
