Mechanism of inactivation of inducible nitric oxide synthase by amidines. Irreversible enzyme inactivation without inactivator modification

Y Zhu, D Nikolic, RB Van Breemen…

Index: Zhu, Yaoqiu; Nikolic, Dejan; Van Breemen, Richard B.; Silverman, Richard B. Journal of the American Chemical Society, 2005 , vol. 127, # 3 p. 858 - 868

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Citation Number: 37

Abstract

Nitric oxide synthases (NOS) are hemoproteins that catalyze the reaction of l-arginine to l- citrulline and nitric oxide. N-(3-(Aminomethyl) benzyl) acetamidine (1400W) was reported to be a slow, tight-binding, and highly selective inhibitor of iNOS in vitro and in vivo. Previous mechanistic studies reported that 1400W was recovered quantitatively after iNOS fully lost its activity and modification to iNOS was not detected. Here, it is shown that 1400W is a time-, ...