Demonstration of the role of scission of the proximal histidine-iron bond in the activation of soluble guanylyl cyclase through metalloporphyrin substitution studies

Elizabeth A. Dierks, Songzhou Hu, Kathleen M. Vogel, Anita E. Yu, Thomas G. Spiro, Judith N. Burstyn

Research output: Contribution to journalArticlepeer-review

80 Scopus citations

Abstract

Activation of soluble guanylyl cyclase (sGC) by NO correlates with scission of the proximal iron-histidine bond, as demonstrated by the application of electronic absorption and resonance Raman spectroscopy to the study of metalloporphyrin-substituted enzymes. The non-native metalloporphyrins, Mn(II)PPIX and Co(II)PPIX, can be introduced into heme-deficient sGC forming five-coordinate complexes. The similarity among Mn(II)sGC, Co(II)sGC, and the corresponding metalloporphyrin-substituted derivatives of Mb and Hb provides confirming evidence for the presence of an axial histidine ligand in sGC. Upon addition of NO, Mn(II)sGC forms a six-coordinate species with the histidine ligand still bound to the Mn, and the enzyme is not activated. In contrast, the Co(II)sGC(NO) adduct is five-coordinate and the enzyme is activated. These data imply that the activated state of sGC is attained when the proximal histidine-metal bond is broken.

Original languageEnglish (US)
Pages (from-to)7316-7323
Number of pages8
JournalJournal of the American Chemical Society
Volume119
Issue number31
DOIs
StatePublished - Aug 6 1997
Externally publishedYes

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

Fingerprint Dive into the research topics of 'Demonstration of the role of scission of the proximal histidine-iron bond in the activation of soluble guanylyl cyclase through metalloporphyrin substitution studies'. Together they form a unique fingerprint.

Cite this