Ligand discrimination in soluble guanylate cyclase and the H-NOX family of heme sensor proteins

Soluble guanylate cyclases (sGCs) are eukaryotic heme sensor proteins that selectively bind NO in the presence of a large excess of the similar diatomic gas, O 2; this discrimination is essential for NO signaling. Recent discoveries place sGC in the H-NOX (heme nitric oxide and/or oxygen binding dom...

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Bibliographic Details
Published in:Current opinion in chemical biology 2005-10, Vol.9 (5), p.441-446
Main Authors: Boon, Elizabeth M, Marletta, Michael A
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Animals
Guanylate Cyclase
Hemeproteins - chemistry
Hemeproteins - metabolism
Humans
Ligands
Molecular Sequence Data
Oxygen - metabolism
Protein Conformation
Receptors, Cytoplasmic and Nuclear - chemistry
Receptors, Cytoplasmic and Nuclear - metabolism
Sequence Homology, Amino Acid
Signal Transduction
Soluble Guanylyl Cyclase
Tyrosine - metabolism
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Summary:Soluble guanylate cyclases (sGCs) are eukaryotic heme sensor proteins that selectively bind NO in the presence of a large excess of the similar diatomic gas, O 2; this discrimination is essential for NO signaling. Recent discoveries place sGC in the H-NOX (heme nitric oxide and/or oxygen binding domain) family that includes bacterial proteins. The defining characteristic of this family is that some H-NOX proteins tightly bind O 2 wheras others, such as sGC, show no measurable affinity for O 2. A molecular basis for this ligand selectivity has now been established. A distal pocket tyrosine is requisite for O 2 binding and is used to kinetically distinguish between NO and O 2. In the absence of this tyrosine, the O 2 dissociation rate is so fast that the O 2 complex is never formed, whereas the rate of NO dissociation remains essentially unchanged, thus providing discrimination.
ISSN:1367-5931
1879-0402
DOI:10.1016/j.cbpa.2005.08.015