Details

Autor(en) / Beteiligte

• Fleury, Fabrice
• Ianoul, Anatoli
• Berjot, Maurice
• Feofanov, Alexei
• Alix, Alain J.P
• Nabiev, Igor

Titel

Camptothecin-binding site in human serum albumin and protein transformations induced by drug binding

Ist Teil von

• FEBS letters, 1997-07, Vol.411 (2), p.215-220

Ort / Verlag

England: Elsevier B.V

Erscheinungsjahr

1997

Quelle

Wiley Online Library - AutoHoldings Journals

Beschreibungen/Notizen

• 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.