Thiols, gold-thiols, zinc-thiols and the redox state of hemoglobin.
The beta subunit of human hemoglobin can be oxidized site-specifically through beta-Cys-93 by Cu(II)(His)2. A series of thiol ligands, gold thiols and zinc(II) inhibit this oxidation. The thiol inhibitors formed a transient ternary intermediate involving Cu(I) with consequent inhibition of electron transfer from the Fe(II)-heme. The intermediate led to the formation of a disulfide at the beta-Cys-93 site. The most effective thiols achieved maximum inhibition at one equivalent per beta heme. Gold thiols and zinc complexes inhibited heme oxidation by competing with the Cu(II)(His)2 for the beta-Cys-93 site.
Potuznik
S
S
Department of Biology, University of California, San Diego, La Jolla.
Gelvan
D
D
Burda
P
P
Saltman
P
P
D001665:Binding Sites; D001667:Binding, Competitive; D003300:Copper / Q000737:chemistry; D003545:Cysteine / Q000737:chemistry; D006046:Gold / Q000737:chemistry; D006454:Hemoglobins / Q000737:chemistry*; D006639:Histidine / Q000494:pharmacology*; D006801:Humans; D009942:Organometallic Compounds / Q000494:pharmacology*; D010084:Oxidation-Reduction / Q000187:drug effects; D013870:Thiomalates / Q000494:pharmacology*; D015032:Zinc / Q000737:chemistry
D006454:Hemoglobins; D009942:Organometallic Compounds; D013870:Thiomalates; C045576:copper bis(histidinate); D006639:Histidine; D006046:Gold; D003300:Copper; D015032:Zinc; D003545:Cysteine