albumin - publications

Predict more albumin - ligand interactions now!

1. Phys Chem Chem Phys. 2012 Jan 23. [Epub ahead of print]

Revealing the ionization ability of binding site I of human serum albumin using
2-(2'-hydroxyphenyl)benzoxazole as a pH sensitive probe.

Abou-Zied OK.

Department of Chemistry, Faculty of Science, Sultan Qaboos University, P.O. Box
36, Postal Code 123, Muscat, Sultanate of Oman.

The ability of site I of human serum albumin (HSA) to bind medium sized molecules
is important for the distribution, metabolism, and efficacy of many drugs.
Herein, we show that this binding site has the ionization ability that may alter
the drug structure during the process of its delivery. We reveal this ability by
employing 2-(2'-hydroxyphenyl)benzoxazole (HBO) as a pH sensitive probe. Binding
of HBO in site I is studied here at physiological pH 7.2 using steady-state and
lifetime spectroscopic measurements, molecular docking and molecular dynamics
(MD) simulation methods. The complex photophysics of HBO and the unique
fluorescence signature of its anionic form indicate that, upon binding with HSA,
the molecule exists in equilibrium between the anionic and the syn-keto forms.
The position of HBO inside the binding site was determined experimentally by
measuring the fluorescence quenching of W214, the sole tryptophan residue in HSA.
The ionization degree of HBO inside the binding site was estimated to be close to
the ionization degree of HBO in an aqueous solution of pH 10. This was concluded
by comparing the fluorescence behavior of bound HBO to that of HBO in different
solvents and in aqueous solutions of different pH values. Molecular docking and
MD simulations show that HBO binds in site I close to W214, confirming the
experimental results, and pinpoint the dominant role of hydrophobic interactions
in the binding site. The formation of the anionic form is proposed to be due to
through-space interaction between the OH group of HBO and both R222 and I290 with
a binding mode similar to that of warfarin in site I. Comparison of the results
with those of HBO mixed with key amino acids in solution indicates the importance
of through-space interaction in the formation of the anion, similar to enzymatic

PMID: 22267206 [PubMed - as supplied by publisher]