Primary Appointment:
 Biochemistry & Biophysics

GEBS Cluster Affiliations:
 Biochemistry, Molecular Biology, & Genetics - BMBG
 Molecular Biophysics and Structural Biochemistry - BSB

University of Rochester
School of Medicine and Dentistry
601 Elmwood Ave, Box 712
Rochester, New York 14642

Medical Center Annex B-104
Phone: (716) 275-8371
E-Mail: Shohei_Koide@urmc.rochester.edu

Lab Web Site

NMR and biophysical studies of protein structure, dynamics, and interactions.

Proteins are responsible for a vast diversity of biological functions, such as chemical catalysis, transport, signal transduction (regulation) and movement. All functions are achieved through unique tree-dimentional (3D) structure and dynamic properties of proteins. I am interested in using high resolution nuclear magnetic resonance (NMR) spectroscopy, in combination with techniques in biophysics, protein chemistry, molecular biology and computational chemistry, to study principles governing structure and dynamics of proteins and structure-function relationships.

Protein folding. The molecular mechanicsm of protein folding, by which a newly synthesized polypeptide chain is folded into a unique 3D structure (the native state), has not yet been fully understood. A goal of my research on protein folding is to characterize at an atomic resolution the 3D structure and dynamics of non-native species (unfolded states and intermediates) present in the folding reaction. The highly flexible nature of these species makes it impossible to crystallize them. State-of-the-art NMR methods coupled with other biophysical techniques, in particular hydrogen exchange labeling, will be applied to effect detailed characterization of folding reactions of small model proteins.

Molecular recognition. One fundamental function of proteins is specific binding. Not only unique 3D structure but also proper dynamic characteristics are essential for achieving specific molecular recognition. I will study the molecular mechanism of protein-ligand interactions. Multidimentional heteronuclear NMR techniques will be applied to determine solution structures of the free protein and protein-ligand complexes, and to characterize dynamic properties of these states. Molecular biology techniques also will be employed to access the contribution of individual amino acid residues to function, structure and dynamics. On the basis of experimental data and theoretical calculations, the research program will be extended to engineer new recognition functions.

Bu, Z., Koide, S. & Engelman, D. M. 1998. A solution SAXS study of Borrelia burgdorferi OspA, a protein containing a single-layer beta-sheet. Protein Science, in press.

Koide, A., Bailey, C. W., Huang, X. & Koide, S. 1998. Fibronecting type III domain as a scaffold for novel ligand binding proteins. J. Mol. Biol., in press.

Huang, X., Yang, X., Luft, B. J., & Koide, S. 1998. NMR identification of epitopes of Lyme disease antigen OspA to monoclonal antibodies.J. Mol. Biol., 281:61-67.

Pham, T. N. and Koide, S. 1998. NMR studies of Borrelia burgdorferi OspA, a 28 kDa protein containing a single-layer beta-sheet.J. Biomol. NMR 11:407-414.

Pham, T.-N., Koide, A. and Koide, S. 1998. A stable single-layer beta-sheet without a hydrophobic core. Nature Struct. Biol. 5:115-119.