Changes of polymerization and conformation of hemoglobin S induced by thiol reagents.
Thiol reagents, covalently bound to cysteine beta 93, either inhibit or facilitate the polymerization process of hemoglobin S. The progelling effect of parahydroxymercurybenzoate or 2,2'-dithiodipyridine contrasted with the increased oxygen affinity and the destabilization of the T state of Hb shown by functional and NMR studies. Thiol reagents increased the oxygen affinity of Hb from 30 to 1000%. Such variability was also observed in the reduction (up to 50%) of the alkaline Bohr effect. We show that the antigelling or progelling activity of thiol reagents does not depend solely on the concentration of molecules present in the deoxy T state but that specific effects of the reagent affects molecular interactions of the hemoglobin S polymerization process.
Garel
M C
MC
INSERM U.91 Hôpital Henri Mondor, Créteil, France.
Caburi-Martin
J
J
Domenget
C
C
Kister
J
J
Craescu
C T
CT
Poyart
C
C
Beuzard
Y
Y
D015082:2,2'-Dipyridyl / Q000031:analogs & derivatives* / Q000494:pharmacology; D000328:Adult; D000755:Anemia, Sickle Cell / Q000097:blood; D004220:Disulfides / Q000494:pharmacology*; D006441:Hemoglobin A / Q000378:metabolism*; D006451:Hemoglobin, Sickle / Q000378:metabolism*; D006801:Humans; D006902:Hydroxymercuribenzoates / Q000494:pharmacology*; D007700:Kinetics; D046911:Macromolecular Substances; D009682:Magnetic Resonance Spectroscopy; D010108:Oxyhemoglobins / Q000378:metabolism; D011487:Protein Conformation; D012016:Reference Values; D013439:Sulfhydryl Reagents / Q000494:pharmacology*
D004220:Disulfides; D006451:Hemoglobin, Sickle; D006902:Hydroxymercuribenzoates; D046911:Macromolecular Substances; D010108:Oxyhemoglobins; D013439:Sulfhydryl Reagents; C030601:4-hydroxymercuribenzoate; C001105:2,2'-dipyridyl disulfide; D015082:2,2'-Dipyridyl; D006441:Hemoglobin A