Biomedical subjects

Luyuan Zhang

Publications and source records attributed to Luyuan Zhang.

4 recordsLinked to original sources

PubMed2006

Femtosecond studies of tryptophan fluorescence dynamics in proteins: local solvation and electronic quenching.

We report our systematic examination of tryptophan fluorescence dynamics in proteins with femtosecond resolution. Distinct patterns of femtosecond-resolved fluorescence transients from the blue to the red side of emission have been characterized to distinguish local ultrafast solvation and electronic quenching. It is shown that tryptophan is an ideal local optical probe for hydration dynamics and protein-water interactions as well as an excellent local molecular reporter for ultrafast electron transfer in proteins, as demonstrated by a series of biological systems, here in melittin, human serum albumin, and human thioredoxin, and at lipid interfaces. These studies clarify the assignments in the literature about the ultrafast solvation or quenching dynamics of tryptophan in proteins. We also report a new observation of solvation dynamics at far red-side emission when the relaxation of the local environment is slower than 1 ps. These results provide a molecular basis for using tryptophan as a local molecular probe for ultrafast protein dynamics in general.

Biophysics↗

PubMed2006

Protein surface hydration mapped by site-specific mutations.

Water motion at protein surfaces is fundamental to protein structure, stability, dynamics, and function. By using intrinsic tryptophans as local optical probes, and with femtosecond resolution, it is possible to probe surface-water motions in the hydration layer. Here, we report our studies of local hydration dynamics at the surface of the enzyme Staphylococcus nuclease using site-specific mutations. From these studies of the WT and four related mutants, which change local charge distribution and structure, we are able to ascertain the contribution to solvation by protein side chains as relatively insignificant. We determined the time scales of hydration to be 3-5 ps and 100-150 ps. The former is the result of local librational/rotational motions of water near the surface; the latter is a direct measure of surface hydration assisted by fluctuations of the protein. Experimentally, these hydration dynamics of the WT and the four mutants are also consistent with results of the total dynamic Stokes shifts and fluorescence emission maxima and are correlated with their local charge distribution and structure. We discuss the role of protein fluctuation on the time scale of labile hydration and suggest reexamination of recent molecular dynamics simulations.

Crystallography, X-Ray↗

PubMed2006

Ultrafast solvation dynamics of human serum albumin: correlations with conformational transitions and site-selected recognition.

Human serum albumin, the most abundant protein found in blood plasma, transports a great variety of ligands in the circulatory system and undergoes reversible conformational transitions over a wide range of pH values. We report here our systematic studies of solvation dynamics and local rigidity in these conformations using a single intrinsic tryptophan (W214) residue as a local molecular probe. With femtosecond resolution, we observed a robust bimodal distribution of time scales for all conformational isomers. The initial solvation occurs in several picoseconds, representing the local librational/rotational motions, followed by the dynamics, in the tens to hundreds of picoseconds, which result from the more bonded water in the tryptophan crevice. Under the physiological condition of neutral pH, we measured approximately 100 ps for the decay of the solvation correlation function and observed a large wobbling motion at the binding site that is deeply buried in a crevice, revealing the softness of the binding pocket and the large plasticity of the native structure. At acidic pH, the albumin molecule transforms to an extended conformation with a large charge distribution at the surface, and a similar temporal behavior was observed. However, at the basic pH, the protein opens the crevice and tightens its globular structure, and we observed significantly faster dynamics, 25-45 ps. These changes in the solvation dynamics are correlated with the conformational transitions and related to their structural integrity.

Crystallography, X-Ray↗

PubMed2005

Ultrafast hydration dynamics in melittin folding and aggregation: helix formation and tetramer self-assembly.

Melittin, an amphipathic peptide from honeybee venom, consists of 26 amino acid residues and adopts different conformations from a random coil, to an alpha-helix, and to a self-assembled tetramer under certain aqueous environments. We report here our systematic studies of the hydration dynamics in these conformations using single intrinsic tryptophan (W19) as a molecular probe. With femtosecond resolution, we observed the solvation dynamics occurring in 0.62 and 14.7 ps in a random-coiled primary structure. The former represents bulklike water motion, and the latter reflects surface-type hydration dynamics of proteins. As a comparison, a model tripeptide (KWK) was also studied. At a membrane-water interface, melittin folds into a secondary alpha-helical structure, and the interfacial water motion was found to take as long as 114 ps, indicating a well-ordered water structure along the membrane surface. In high-salt aqueous solution, the dielectric screening and ionic solvation promote the hydrophobic core collapse in melittin aggregation and facilitate the tetramer formation. This self-assembled tertiary structure is also stabilized by the strong hydrophilic interactions of charged C-terminal residues and associated ions with water molecules in the two assembled regions. The hydration dynamics was observed to occur in 87 ps, significantly slower than typical water relaxation at protein surfaces but similar to water motion at membrane interfaces. Thus, the observed time scale of approximately 100 ps probably implies appropriate water mobility for mediating the formation of high-order structures of melittin in an alpha-helix and a self-assembled tetramer. These results elucidate the critical role of hydration dynamics in peptide conformational transitions and protein structural stability and integrity.

Amino Acid Sequence↗