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

FEBS Lett. 1997 Jul 14;411(2-3):215-20. doi: 10.1016/s0014-5793(97)00693-5.

Abstract

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 interdomain connections within the IIA structural domain of HSA and it induces relative movement of the protein structural domains.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Binding, Competitive
  • Camptothecin / metabolism*
  • Camptothecin / pharmacology
  • Circular Dichroism
  • Disulfides / metabolism
  • Humans
  • Protein Binding
  • Protein Conformation
  • Protein Structure, Secondary
  • Serum Albumin / chemistry*
  • Serum Albumin / metabolism*
  • Spectrum Analysis, Raman
  • Tryptophan / metabolism

Substances

  • Disulfides
  • Serum Albumin
  • Tryptophan
  • Camptothecin