Ultrafast Solvation Dynamics of Human Serum Albumin:Correlation with Conformational Transitions

and Site-Selected Recognition

Weihong Qiu, Luyuan Zhang, Oghaghare Okobiah, Yi Yang, Lijuan Wang, Ahmed H. Zewail and Dongping Zhong

Biophysics ProgramThe Ohio State University

Tryptophan: the Most Appropriate Tryptophan: the Most Appropriate Fluorescence Probe in ProteinsFluorescence Probe in Proteins

• No concerns of spatial uncertainty

• Allow single-residue spatial resolution

• Easy incorporation in proteins with site-

directed mutagenesis method

Conformational Transitions E F N B A pH Values 2.7 4.3 8 10.0

Human Serum Albumin: Remarkable Drug Delivery Machinery & pH-Dependent Conformation Transition

Solvation Dynamics: the Concept

Pal, S.K.; Peon, J.; Bagchi, B. and Zewail, A.H. J.Phys. Chem. B 2002, 106, 12376

Femtosecond Up-Conversion Apparatus

Human Serum Albumin: Normal Form

Human Serum Albumin: Fast-Migrating Form

Human Serum Albumin: Extended Form

Conformation-Dependent Solvation Dynamics

Femtosecond-Resolved Rotational Anisotropy

Tryptophan residue has the largest rotational freedom in N-form HSA

Conformational Transitions and Solvation Dynamics: the Correlation

108 ps 186 ps 133 ps 46 ps 27 ps

ConclusionsConclusions

• We found the ligand-binding pocket is highly We found the ligand-binding pocket is highly flexible.flexible.

• We established the correlation between the We established the correlation between the conformational transition of HSA and the conformational transition of HSA and the observed solvation dynamics at the ligand-observed solvation dynamics at the ligand-binding pocket.binding pocket.

Acknowledgements

Dr. Dongping ZhongDr. Ahmed H. ZewailLuyuan ZhangOghaghare OkobiahYi Yang Lijuan Wang Petroleum Research Foundation National Science Foundation