title: Basis of guanylate cyclase activation by carbon monoxide.
abstract: Kinetics of CO association with guanylate cyclase [GTP pyrophosphate-lyase (cyclizing), EC 4.6.1.2] and dissociation from carboxy guanylate cyclase have been studied at pH 7.5 by flash photolysis, yielding rate constants at 23 degrees C of 1.2 +/- 0.1 x 10(5) M-1.sec-1 and 28 +/- 2 sec-1, respectively. While the CO combination rate constant is the same as for the T state of hemoglobin, the CO dissociation rate constant is much higher than expected for a six-coordinate carboxyheme protein; yet the absorption spectrum is indicative of a six-coordinate heme. The two observations are reconciled by a reaction mechanism in which CO dissociation proceeds via a five-coordinate intermediate. This intermediate is structurally very similar to the five-coordinate nitrosyl heme derivative of guanylate cyclase and is presumably responsible for the observed 4-fold activation of guanylate cyclase by CO. Thus, we provide a model that explains enzyme activities of the nitrosyl and carboxy forms of the enzyme on the basis of a common mechanism.
authors.affiliation: Department of Medicine, University of California, San Diego, La Jolla 92093-0652, USA.
authors.forename: V G
authors.initials: VG
authors.lastname: Kharitonov
authors.forename: V S
authors.initials: VS
authors.lastname: Sharma
authors.forename: R B
authors.initials: RB
authors.lastname: Pilz
authors.forename: D
authors.initials: D
authors.lastname: Magde
authors.forename: D
authors.initials: D
authors.lastname: Koesling
mesh_terms: D000818:Animals; D001665:Binding Sites; D002248:Carbon Monoxide / Q000494:pharmacology*; D002417:Cattle; D004789:Enzyme Activation; D006162:Guanylate Cyclase / Q000737:chemistry* / Q000378:metabolism*; D006418:Heme / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008168:Lung / Q000201:enzymology; D012709:Serum Albumin / Q000737:chemistry / Q000378:metabolism; D013053:Spectrophotometry; D013997:Time Factors
chemical_list: D012709:Serum Albumin; D006418:Heme; D002248:Carbon Monoxide; D006162:Guanylate Cyclase