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Camptothecin‐binding site in human serum albumin and protein transformations induced by drug binding
Author(s) -
Fleury Fabrice,
Ianoul Anatoli,
Berjot Maurice,
Feofanov Alexei,
Alix Alain J.P,
Nabiev Igor
Publication year - 1997
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(97)00693-5
Subject(s) - human serum albumin , chemistry , camptothecin , binding site , circular dichroism , binding domain , stereochemistry , plasma protein binding , protein structure , structural similarity , serum albumin , biophysics , biochemistry , biology
Circular dichroism (CD) and Raman spectroscopy were employed in order to locate a camptothecin (CPT)‐binding site within human serum albumin (HSA) and to identify protein structural transformations induced by CPT binding. A competitive binding of CPT and 3′‐azido‐3′‐deoxythymidine (a ligand occupying IIIA structural sub‐domain of the protein) to HSA does not show any competition and demonstrates that the ligands are located in the different binding sites, whereas a HSA‐bound CPT may be replaced by warfarin, occupying IIA structural sub‐domain of the protein. Raman and CD spectra of HSA and HSA/CPT complexes show that the CPT‐binding does not induce changes of the global protein secondary structure. On the other hand, Raman spectra reveal pronounced CPT‐induced local structural modifications of the HSA molecule, involving changes in configuration of the two disulfide bonds and transfer of a single Trp‐residue to hydrophilic environment. These data suggest that CPT is bound in the region of inter‐domain connections within the IIA structural domain of HSA and it induces relative movement of the protein structural domains.