title: Coupling of disulfide bond and distal histidine dissociation in human ferrous cytoglobin regulates ligand binding.
abstract: Earlier kinetics studies on cytoglobin did not assign functional properties to specific structural forms. Here, we used defined monomeric and dimeric forms and cysteine mutants to show that an intramolecular disulfide bond (C38-C83) alters the dissociation rate constant of the intrinsic histidine (H81) (∼1000 fold), thus controlling binding of extrinsic ligands. Through time-resolved spectra we have unequivocally assigned CO binding to hexa- and penta-coordinate forms and have made direct measurement of histidine rebinding following photolysis. We present a model that describes how the cysteine redox state of the monomer controls histidine dissociation rate constants and hence extrinsic ligand binding.
authors.affiliation: School of Biological Sciences, University of Essex, Wivenhoe Park, Colchester, Essex CO4 3SQ, United Kingdom.
authors.forename: Penny
authors.initials: P
authors.lastname: Beckerson
authors.affiliation: School of Biological Sciences, University of Essex, Wivenhoe Park, Colchester, Essex CO4 3SQ, United Kingdom. Electronic address: reedb@essex.ac.uk.
authors.forename: Brandon J
authors.initials: BJ
authors.lastname: Reeder
authors.affiliation: School of Biological Sciences, University of Essex, Wivenhoe Park, Colchester, Essex CO4 3SQ, United Kingdom.
authors.forename: Michael T
authors.initials: MT
authors.lastname: Wilson
mesh_terms: D002248:Carbon Monoxide / Q000737:chemistry*; D003553:Cystine / Q000737:chemistry; D000078842:Cytoglobin; D005296:Ferrous Compounds / Q000737:chemistry; D005914:Globins / Q000737:chemistry*; D006639:Histidine / Q000737:chemistry*; D006801:Humans; D007700:Kinetics; D008024:Ligands; D008958:Models, Molecular; D010084:Oxidation-Reduction; D011485:Protein Binding
chemical_list: C000627265:CYGB protein, human; D000078842:Cytoglobin; D005296:Ferrous Compounds; D008024:Ligands; D003553:Cystine; D006639:Histidine; D002248:Carbon Monoxide; D005914:Globins
keywords: Biphasic; Carbon monoxide; Cysteine; Cytoglobin; Dimer; Distal histidine; Disulfide; Ferrous; Flash photolysis; Monomer