Involvement of a lysine residue in the N-terminal Ni2+ and Cu2+ binding site of serum albumins. Comparison with Co2+, Cd2+ and Al3+.
We report one-dimensional and two-dimensional 1H-NMR studies of the binding of Ni2+, Cu2+, Co2+, Cd2+ and Al3+ to defatted bovine and human serum albumins. The diamagnetic shifts induced by Ni2+, and paramagnetic effects due to Cu2+, were consistent with strong binding to a square-planar site formed by the three N-terminal amino acid residues (Asp-Thr-His for bovine, and Asp-Ala-His for human albumin). In contrast to previous studies on isolated 1-24 N-terminal peptide, a Lys residue also appeared to be involved in the binding site, and is assigned as Lys4. A second His residue is also close to the Cu2+/Ni2+ binding site in bovine serum albumin and is assigned to His59 (not present in human albumin). Co2+ caused specific perturbation of the resonances for the three N-terminal residues as well as those for Lys4. This is the first evidence for Co2+ binding to the N-terminal metal site of serum albumin. Neither Al3+ nor Cd2+ perturbed resonances for the N-terminal amino acids, but bind elsewhere in the protein.
Sadler
P J
PJ
Christopher Ingold Laboratories, University of London, England.
Tucker
A
A
Viles
J H
JH
D000535:Aluminum / Q000378:metabolism; D000818:Animals; D001665:Binding Sites; D002104:Cadmium / Q000378:metabolism; D002417:Cattle; D003035:Cobalt / Q000378:metabolism; D003300:Copper / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D008239:Lysine / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D015394:Molecular Structure; D009532:Nickel / Q000378:metabolism*; D012709:Serum Albumin / Q000737:chemistry* / Q000378:metabolism*; D012710:Serum Albumin, Bovine / Q000737:chemistry / Q000378:metabolism
D012709:Serum Albumin; D002104:Cadmium; D012710:Serum Albumin, Bovine; D003035:Cobalt; D003300:Copper; D009532:Nickel; D000535:Aluminum; D008239:Lysine