Russian Journal

ISSN 0042-8809

Issue:
Volume 45, issue 3

Title:
MECHANISMS REGULATION ACTIVITY OF NITRIC OXIDE SYNTHASE BY CALMODULIN: A REVEIW

Authors: Yu.V.Gervaziev, N.N.Sokolov.

Address: Institute of Biomedical Chemistry RAMS, Pogodinskaya str. 10, 119832 Moscow; fax: (095) 245-0857

Abstract:

The Ca²⁺-calmodulin system controls the neuronal and endotelial isoforms of NOS, whereas the inducible isoform is calcium independent apparently because CaM is a tightly bound subunit of iNOS. The canonical CaM-binding site is located between the oxygenase and reductase NOS domains. CaM controls eNOS dimerization rather then iNOS one. The proteins with the so-called “IQ” motif bind calmodulin in a Ca²⁺-independent manner. This group of proteins does not include iNOS, which has the canonical CaM-binding motif. In the experiments with synthetic peptides was demonstrated that the interaction between the calmodulin and CaM-binding site of iNOS does not depend on the Ca²⁺ concentration. On the other hand, in the experiments with fusion, mutant and truncated NOSs was shown that these features of CaM-binding region of iNOS is not enough for the enzyme to bind calmodulin Ca²⁺-independently; this interaction requiers the additional binding sites both in reductase and oxygenase domains of iNOS. In the experiments with fusion calmodulins the mechanism of calmodulin regulation of electron transfer in NOS was elaborated. The concept of autoinhibitory control element in the FMN-binding site of constitutive NOS is discussed.

Key words: nitric oxide synthase, isoforms of nitric oxide synthase, calmodulin, domain structure of nitric oxide synthase, regulation activity of nitric oxide synthase.

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