Conformational changes induced in bovine serum albumin by the photodynamic action of haematoporphyrin.
The photodynamic action of haematoporphyrin upon bovine serum albumin, spin-labelled at the cysteine-34 residue, has been shown to: (i) increase its susceptibility to proteolysis by chymotrypsin and trypsin, and (ii) increase its susceptibility to denaturation by urea. This is thought to be the result of conformational changes caused by the formation of protein radicals, although contributions from subsequent radical reactions of, for example, amino acids, may also take place. Such species have previously been shown, by EPR spin-trapping, to be formed in this system. Increased proteolytic susceptibility of non spin-labelled protein is also observed upon photolysis with haematoporphyrin, indicating that the changes observed in the spin-labelled protein also occur in the native form, and are not artefactual in nature. The significance of these photochemically-induced conformational changes within proteins in the photodynamic therapy of tumours, and other protein-radical systems is discussed.
Timmins
G S
GS
Department of Chemistry, University of York, Heslington, UK.
Davies
M J
MJ
D000595:Amino Acid Sequence; D003198:Computer Simulation; D003545:Cysteine; D004578:Electron Spin Resonance Spectroscopy; D005609:Free Radicals; D006415:Hematoporphyrins / Q000494:pharmacology*; D007700:Kinetics; D008969:Molecular Sequence Data; D010782:Photolysis; D011487:Protein Conformation / Q000187:drug effects*; D011489:Protein Denaturation; D012710:Serum Albumin, Bovine / Q000737:chemistry* / Q000187:drug effects; D014508:Urea / Q000494:pharmacology
D005609:Free Radicals; D006415:Hematoporphyrins; D012710:Serum Albumin, Bovine; D014508:Urea; D003545:Cysteine