Patent ID: 7214519

Claim:
A method of screening a substance of interest for heme independent modulation of enzymatic activity of soluble guanylyl cyclase (sGC) comprising: a) obtaining purified αβ Cys105 mutant soluble guanylyl cyclase enzyme or a cell lysate containing αβ Cys105 mutant soluble guanylyl cyclase enzyme; b) determining activity of said purified enzyme or cell lysate for forming cGMP from GTP in a reaction medium in the presence of said substance; c) determining activity of said purified enzyme or cell lysate for forming cGMP from GTP in a reaction medium in the absence of said substance; optionally, d) carrying out steps b) and c) in the presence of an activator other than said substance; e) comparing the determinations horn b) and c), and, d), if present, to yield a comparison result; and f) assessing the activity of said substance to modulate cGMP production by said purified enzyme or cell lysate from the value of said comparison result, wherein increased or decreased formation of cGMP in the presence of said substance indicates that said substance is active for modulating heme independent cGMP production.