Hydrogen sulfide stimulates the catalytic activity of a heme-regulated phosphodiesterase from Escherichia coli (Ec DOS)

Abstract

Ec DOS, a heme-regulated phosphodiesterase from Escherichia coli, is an oxygen sensor enzyme composed of a heme-bound O2 sensor domain at the N-terminus and a catalytic domain at the C-terminus. The catalytic activity of Ec DOS is substantially enhanced with the formation of a Fe(II) heme-O2 complex. The physiological importance of H2S as a fourth signaling gas molecule in addition to O2, CO and NO is an emerging focus of research, since H2S participates in various physiological functions. In the present study, we showed that catalysis by Ec DOS is markedly increased by H2S under aerobic conditions. Absorption spectral findings suggest that SH−-modified heme iron complexes, such as Fe(III)–SH− and Fe(II)–O2 complexes, represent the active species for H2S-induced catalysis. We further examined the role of Cys residues in H2S-induced catalysis using Cys→Ala mutant enzymes. Based on the collective data, we speculate that H2S-induced catalytic enhancement is facilitated by an admixture of Fe(III)–SH− and Fe(II)–O2 complexes formed during catalysis and modification of specific Cys residue(s) in the catalytic domain.