title: Highly reactive cysteine residues in rodent hemoglobins.
abstract: Two hemoglobins with cysteine residues highly reactive toward electrophiles have been identified and characterized. Cys-125beta of guinea pig hemoglobin has a low pK(a) and forms conjugates with electrophiles more quickly than glutathione and several orders of magnitude more quickly than other protein thiols. This cysteine is capable of intercepting benzoquinone, a known carcinogenic metabolite, before other protein nucleophiles can be modified. Cys-13beta of mouse hemoglobin was observed to conjugate with electrophiles as quickly as glutathione. The structural basis of reactivity is different in the two hemoglobins and is analyzed in terms of hydrogen-bonding, solvent accessibility, and helix-dipole contributions. Complementing a previously characterized highly reactive cysteine in rat hemoglobin, identification of these cysteines suggests that the reactivity of these hemoglobins could represent a common function as a detoxification sink against carcinogens.
authors.affiliation: Department of Chemistry, Reed College, Portland, Oregon 97202, USA.
authors.forename: J J
authors.initials: JJ
authors.lastname: Miranda
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D003545:Cysteine / Q000378:metabolism*; D006168:Guinea Pigs; D006454:Hemoglobins / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D051379:Mice; D008969:Molecular Sequence Data; D051381:Rats; D017207:Rats, Sprague-Dawley; D017386:Sequence Homology, Amino Acid
chemical_list: D006454:Hemoglobins; D003545:Cysteine