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

FEBS Letters

Feofanov, Alexei³  Fleury, Fabrice²  Alix, Alain J.P¹  Ianoul, Anatoli²  Nabiev, Igor²  Berjot, Maurice¹ 

[1] Laboratoire de Spectroscopies et Structures Biomoléculaires, UFR Sciences, Université de Reims Champagne-Ardenne/INSERM Unité 314, 51687 Reims Cedex, France;Laboratoire de Spectroscopie Biomoléculaire, UFR de Pharmacie, Université de Reims Champagne-Ardenne, 51096 Reims Cedex, France;Optical Spectroscopy Division, Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117871 Moscow, Russia

关键词: Raman spectroscopy;    Circular dichroism;    Topoisomerase inhibitor;    Camptothecin;    Human serum albumin;    20(S)-CPT or CPT;    20(S)-camptothecin;    HSA;    human serum albumin;    BSA;    bovine serum albumin;    CD;    circular dichroism;    AZT;    azido-3′-deoxythymidine;    DMSO;    dimethylsulfoxide;    PBS;    potassium-buffered saline;    Topo I;    DNA topoisomerase I;   

DOI  :  10.1016/S0014-5793(97)00693-5

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown