Key result
nNOS Trp409 mutations drive hyperactivity via ~7-fold faster heme-NO complex decay.
Why the study?
Mutation of Trp(409) in neuronal NO synthase causes hyperactive NO synthesis and less heme-NO complex buildup, but the underlying mechanism was unclear.
Mutant hyperactivity in neuronal NO synthase derives from slower formation and faster decay of the heme-NO complex, minimizing partitioning into the NO-bound form.
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Trp409 mutation enhances nNOS activity in vitro; hypothesis-generating for NO signaling in cardiovascular disease.
Adak et al. (2000) studied this question. Mutation of Trp(409) to Phe or Tyr in neuronal NO synthase vs. Wild type nNOS was evaluated on Kinetics of heme-NO complex formation and decay. Mutation of Trp(409) to Phe or Tyr in neuronal NO synthase causes hyperactivity due to slower formation (3-5 times slower) and faster decay (7 times faster) of the heme-NO complex.
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