Assembly and activation of heme-deficient neuronal NO synthase with various porphyrins

Andrew T. Bender, Yasuhiko Kamada, Patricia A. Kleaveland, Yoichi Osawa

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)


The heme prosthetic group of NO synthase is critical for catalytic activity as well as assembly of the enzyme to the native homodimeric form. In the current study, we examined if structurally different metal porphyrins could substitute for the native heme prosthetic group in neuronal NO synthase (nNOS) with regard to assembly and catalysis. We established, with the use of a recently developed in vitro method that functionally reconstitutes heme-deficient apo-nNOS, that Fe-mesoporphyrin IX or Fe-deuteroporphyrin IX can substitute for heme and lead to assembly of a functional nNOS, albeit with lower activity. Fe-protoporphyrin IX dimethyl ester or the metal free protoporphyrin IX, however, lead to minimal assembly of nNOS. Protoporphyrin IX compounds where the native Fe was substituted with Zn, Mn, Co, or Sn lead to assembly of nNOS, but no detectable NO was synthesized in the presence of NADPH and L-arginine. Thus, the presence of the metal and propionic acid groups, but not the vinyl moieties, of heme are important structural features in assembly of nNOS. These studies establish that the mechanism of assembly and catalysis of nNOS can be probed with structurally diverse metal porphyrins.

Original languageEnglish
Pages (from-to)625-634
Number of pages10
JournalJournal of Inorganic Biochemistry
Issue number4
Publication statusPublished - Sep 20 2002
Externally publishedYes


  • Assembly
  • Dimerization
  • Heme
  • Hemoprotein
  • Nitric oxide
  • Nitric oxide synthase
  • Porphyrin

ASJC Scopus subject areas

  • Biochemistry
  • Inorganic Chemistry


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