Water participation in molecular recognition and protein-ligand association: Probing the drug binding site "Sudlow I" in human serum albumin

Najla Al-Lawatia, Thomas Steinbrecher, Osama K. Abou-Zied

Research output: Chapter in Book/Report/Conference proceedingConference contribution

7 Citations (Scopus)

Abstract

Human serum albumin (HSA) plays an important role in the transport and disposition of endogenous and exogenous ligands present in blood. Its capacity to reversibly bind a large variety of drugs results in its prevailing role in drug pharmacokinetics and pharmacodynamics. In this work, we used 7-hydroxyquinoline (7HQ) as a probe to study the binding nature of one of the major drug binding sites of HSA (Sudlow I) and to reveal the local environment around the probe in the binding site. The interaction between 7HQ and HSA at a physiological pH of 7.2 was investigated using steady-state and lifetime spectroscopic measurements, molecular docking and molecular dynamics (MD) simulations methods. The fluorescence results indicate a selective interaction between 7HQ and the Trp214 residue. The reduction in both the intensity and lifetime of the Trp214 fluorescence upon probe binding indicates the dominant role of static quenching. Molecular docking and MD simulations show that 7HQ binds in Sudlow site I close to Trp214, confirming the experimental results, and pinpoint the dominant role of hydrophobic interaction in the binding site. Electrostatic interactions were also found to be important in which two water molecules form strong hydrogen bonds with the polar groups of 7HQ. Detection of water in the binding site agrees with the absorption and fluorescence results that show the formation of a zwitterion tautomer of 7HQ. The unique spectral signatures of 7HQ in water make this molecule a potential probe for detecting the presence of water in nanocavities of proteins. Interaction of 7HQ with water in the binding site shows that water molecules can be crucial for molecular recognition and association in protein binding sites.

Original languageEnglish
Title of host publicationProgress in Biomedical Optics and Imaging - Proceedings of SPIE
Volume8233
DOIs
Publication statusPublished - 2012
EventReporters, Markers, Dyes, Nanoparticles, and Molecular Probes for Biomedical Applications IV - San Francisco, CA, United States
Duration: Jan 23 2012Jan 25 2012

Other

OtherReporters, Markers, Dyes, Nanoparticles, and Molecular Probes for Biomedical Applications IV
CountryUnited States
CitySan Francisco, CA
Period1/23/121/25/12

Fingerprint

Molecular recognition
Binding sites
albumins
Serum Albumin
serums
drugs
Binding Sites
Ligands
Association reactions
proteins
Proteins
ligands
Water
Pharmaceutical Preparations
water
probes
Fluorescence
fluorescence
Molecules
interactions

Keywords

  • 7-Hydroxyquinoline
  • Biological probes
  • Drug binding sites
  • Human serum albumin
  • Ligand docking
  • Molecular dynamics simulations

ASJC Scopus subject areas

  • Atomic and Molecular Physics, and Optics
  • Electronic, Optical and Magnetic Materials
  • Biomaterials
  • Radiology Nuclear Medicine and imaging

Cite this

Al-Lawatia, N., Steinbrecher, T., & Abou-Zied, O. K. (2012). Water participation in molecular recognition and protein-ligand association: Probing the drug binding site "Sudlow I" in human serum albumin. In Progress in Biomedical Optics and Imaging - Proceedings of SPIE (Vol. 8233). [82331D] https://doi.org/10.1117/12.905809

Water participation in molecular recognition and protein-ligand association : Probing the drug binding site "Sudlow I" in human serum albumin. / Al-Lawatia, Najla; Steinbrecher, Thomas; Abou-Zied, Osama K.

Progress in Biomedical Optics and Imaging - Proceedings of SPIE. Vol. 8233 2012. 82331D.

Research output: Chapter in Book/Report/Conference proceedingConference contribution

Al-Lawatia, N, Steinbrecher, T & Abou-Zied, OK 2012, Water participation in molecular recognition and protein-ligand association: Probing the drug binding site "Sudlow I" in human serum albumin. in Progress in Biomedical Optics and Imaging - Proceedings of SPIE. vol. 8233, 82331D, Reporters, Markers, Dyes, Nanoparticles, and Molecular Probes for Biomedical Applications IV, San Francisco, CA, United States, 1/23/12. https://doi.org/10.1117/12.905809
Al-Lawatia, Najla ; Steinbrecher, Thomas ; Abou-Zied, Osama K. / Water participation in molecular recognition and protein-ligand association : Probing the drug binding site "Sudlow I" in human serum albumin. Progress in Biomedical Optics and Imaging - Proceedings of SPIE. Vol. 8233 2012.
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