Neuronal no synthase interaction with calmodulintroponin C chimeras: Divergent activation of catalytic functions and its relationship to reduction of flavin or heme centers
Calmodulin (CaM) activates neuronal nitric oxide synthase (nNOS) catalytic functions and upregulates electron transfer into its flavin and heme centers. We utilized CaM-troponin C chimeras which variably activate nNOS NO synthesis to examine the relationship between CaM domain structure, activation of catalysis. and control of internal electron transfer at two points in nNOS. CaM chimeras singly substituted with troponin C domains 4, .V 2, or 1 were increasingly unable to activate nNOS NO synthesis, but all activated some cytochromc e reduction. Activation of NO synthesis was related to the rate of heme iron reduction stimulated by each chimera, which varied from O-SO'/t compared to CaM. In contrast, augmentation of cylochrome c reduction was not always associated with accelerated flavin reduction. CaM structural requirements for activating nNOS flavin or heme iron reduction were similar and were more stringent than for enhancing cytochrome c reduction. Thus. CaM control- NO synthesis by governing herne iron reduction, but may enhance reductase activity by two mechanisms, only one of which is associated with an increased rate of flavin reduction.
Gachhui, R; Abu-Soud, HM; Ghosh, DK; Presta, A; Blazing, MA; Mayert, B; George, SE; Stuehrt, DJ
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