A new paradigm for gaseous ligand selectivity of hemoproteins highlighted by soluble guanylate cyclase

• Published in: Journal of inorganic biochemistry Vol. 214; p. 111267
• Main Authors: Wu, Gang, Martin, Emil, Berka, Vladimir, Liu, Wen, Garcin, Elsa D., Tsai, Ah-Lim
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.01.2021; Elsevier
• Subjects: Biochemistry, Molecular Biology; Biophysics; Carbon Monoxide - chemistry; Carbon Monoxide - metabolism; Chemical Sciences; Gas sensor/binding hemoproteins; Gaseous ligand selectivity; Hemeproteins - chemistry; Hemeproteins - metabolism; Inorganic chemistry; Life Sciences; Nitric Oxide - chemistry; Nitric Oxide - metabolism; Oxygen - chemistry; Oxygen - metabolism; Sliding scale rule; Soluble guanylate cyclase; Soluble Guanylyl Cyclase - chemistry; Soluble Guanylyl Cyclase - metabolism; Sliding scale rule; Gaseous ligand selectivity; Soluble guanylate cyclase; Gas sensor/binding hemoproteins
• ISSN: 0162-0134; 1873-3344
• DOI: 10.1016/j.jinorgbio.2020.111267

Nitric oxide (NO), carbon monoxide (CO), and oxygen (O2) are important physiological messengers whose concentrations vary in a remarkable range, [NO] typically from nM to several μM while [O2] reaching to hundreds of μM. One of the machineries evolved in living organisms for gas sensing is sensor hemoproteins whose conformational change upon gas binding triggers downstream response cascades. The recently proposed “sliding scale rule” hypothesis provides a general interpretation for gaseous ligand selectivity of hemoproteins, identifying five factors that govern gaseous ligand selectivity. Hemoproteins have intrinsic selectivity for the three gases due to a neutral proximal histidine ligand while proximal strain of heme and distal steric hindrance indiscriminately adjust the affinity of these three gases for heme. On the other hand, multiple-step NO binding and distal hydrogen bond donor(s) specifically enhance affinity for NO and O2, respectively. The “sliding scale rule” hypothesis provides clear interpretation for dramatic selectivity for NO over O2 in soluble guanylate cyclase (sGC) which is an important example of sensor hemoproteins and plays vital roles in a wide range of physiological functions. The “sliding scale rule” hypothesis has so far been validated by all experimental data and it may guide future designs for heme-based gas sensors. The gaseous ligand selectivity of soluble guanylate cyclase (sGC) obeys the “sliding scale rule”. sGC excludes oxygen binding through the proximal strain of heme and enhanced affinity for NO by multiple-step NO binding. [Display omitted] •Proximal ligand, heme proximal strain and distal steric hindrance govern gas binding.•Distal hydrogen bonding enhances O2 affinity; multiple-step binding boosts NO affinity.•Proximal strain excludes O2 binding from soluble guanylate cyclase (sGC).•Multiple-step NO binding enables sGC efficient NO sensing.•“Sliding scale rule” provides insights into ‘deactivation’ and ‘reactivation’ of sGC.