Platinum(II) binding to metallothioneins.
The reaction of equine renal metallothionein (MT) with excess K2PtCl4 at pH 2 results in a polymeric adduct containing 17 +/- 2 mol Pt/mol MT. A monomeric adduct containing 7 mol Pt/mol MT is obtained at neutral pH. Rates of reaction of Pt7MT with DTNB and iodoacetic acid are consistent with Pt2+ to cysteine thiolate coordination, and the extent of reaction in both cases is 11 +/- 2 mol cys/mol MT. Adducts from the reaction of K2PtCl4 with apoMT chemically modified at the N-terminal methionine residue, Cd7MT, and native MT are also reported. A structural model of Pt7MT is proposed in which the square planar tetrathiolate Pt(II) unit is incorporated into a three-metal beta cluster. Implications for the metabolism of platinum anticancer drugs are discussed.
Bongers
J
J
Department of Chemistry, University of Florida, Gainesville 32611.
Bell
J U
JU
Richardson
D E
DE
D000818:Animals; D002942:Circular Dichroism; D006736:Horses; D007668:Kidney / Q000378:metabolism; D007700:Kinetics; D008668:Metallothionein / Q000378:metabolism*; D010984:Platinum / Q000378:metabolism*; D017671:Platinum Compounds; D011485:Protein Binding; D011487:Protein Conformation
D017671:Platinum Compounds; C030173:platinum chloride; D010984:Platinum; D008668:Metallothionein