Interaction of hypericin with serum albumins: Surface-enhanced Raman spectroscopy, resonance Raman spectroscopy and molecular modeling study

Surface-enhanced Raman spectroscopy, resonance Raman spectroscopy and molec ular modeling were employed to study the interaction of hypericin (Hyp) wit h human (HSA), rat (RSA) and bovine (BSA) serum albumins. The identificatio n of the binding site of Hyp in serum albumins as well as the structural mo del for Hyp/HSA complex are presented. The interactions mainly reflect: (1) a change of the strength of H bonding at the N1-H site of Trp; (2) a chang e of the Trp side-chain conformation; (3) a change of the hydrophobicity of the Trp environment; and (4) a formation of an H-bond between the carbonyl group of Hyp and a proton donor in HSA and RSA which leads to a protonated -like carbonyl in Hyp. Our results indicate that Hyp is rigidly bound in II A subdomain of HSA close to Trp214 (distance 5.12 Angstrom between the cent ers of masses). In the model presented the carbonyl group of Hyp is hydroge n bonded to Asn458. Two other candidates for hydrogen bonds have been ident ified between the bay-region hydroxyl group of Hyp and the carbonyl group o f the Trp214 peptidic link and between the peri-region hydroxyl group of Hy p and the Asn458 carbonyl group. It is shown that the structures of the Hyp /HSA and Hyp/RSA complexes are similar to, and in some aspects different fr om, those found for the Hyp/BSA complex. The role of aminoacid sequence in the IIA subdomains of HSA, RSA and BSA is discussed to explain the observed differences.