Allosteric and binding properties of Asp1-Glu382 truncated recombinant human serum albumin - An optical and NMR spectroscopic investigation

Gabriella Fanali, Giorgio Pariani, Paolo Ascenzi, Mauro Fasano

Research output: Contribution to journalArticle

Abstract

Human serum albumin (HSA) is known for its exceptional ligand-binding capacity; indeed, its modular domain organization provides a variety of ligand-binding sites. Its flexible modular structure involves more than the immediate vicinity of the binding site(s), affecting the ligand-binding properties of the whole protein. Here, biochemical characterization by 1H-NMR relaxometry and optical spectroscopy of a truncated form of HSA (tHSA) encompassing domains I and II (Asp1-Glu382) is reported. Removal of the C-terminal domain III results in a number of contacts that involve domain I (containing the heme site) and domain II (containing the warfarin site) being lost; however, the allosteric linkage between heme and warfarin sites is maintained. tHSA shows a nuclear magnetic relaxation dispersion profile similar to that of HSA, and displays increased affinity for ibuprofen, warfarin, and heme, suggesting that the fold is preserved. Moreover, the allosteric properties that make HSA a peculiar monomeric protein and account for the regulation of ligand-binding modes by heterotropic interactions are maintained after removal of domain III. Therefore, tHSA is a valuable model with which to investigate allosteric properties of HSA, allowing independent analysis of the linkages between different drug-binding sites.

Original languageEnglish
Pages (from-to)2241-2250
Number of pages10
JournalFEBS Journal
Volume276
Issue number8
DOIs
Publication statusPublished - Apr 2009

Keywords

  • Human serum albumin
  • Ibuprofen
  • Nuclear magnetic relaxation dispersion
  • Truncated human serum albumin
  • Warfarin

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Fingerprint Dive into the research topics of 'Allosteric and binding properties of Asp1-Glu382 truncated recombinant human serum albumin - An optical and NMR spectroscopic investigation'. Together they form a unique fingerprint.

  • Cite this