Proteins are the building blocks for all life forms. They are produced in ribosomes as non-structured nascent polypeptides, which subsequently fold into functional proteins with well defined three-dimensional structures. 

The first goal of our research program is to study the structure and function relationships in various hemoglobins from unicellular organisms.  They include two truncated hemoglobins from Mycobacterium tuberculosis, a flavohemoglobin from E. coli and two hemoglobins (a truncated hemoglobin and a flavohemoglobin) from Campylobacter Jejuni. Biochemical and biophysical techniques are currently being carried out to uncover the physiological functions and the related reaction mechanisms of these hemoglobins.

The second goal of our research program is to understand the pathways of protein folding. With cytochrome c as a model system, we discovered that the folding of a small single domain protein involves two phases. The first phase involves the collapsing of the unstructured polypeptide chain to a semi-compact molten globule-like structure. In the second phase, it is followed by fine-tuning of the polypeptide architecture through a thermodynamically controlled process. This biphasic mechanism guarantees the efficiency and fidelity of the folding process. The current focus is to dissect the folding pathway of myoglobin and intestinal fatty acid binding proteins to test the generality of this model.

In this research program, a wide array of spectroscopic tools, including optical absorption, fluorescence, circular dichroism and UV / VIS reasonace Raman scattering, are utilized to follow various biological processes. With the state-of-the-art rapid solution mixing techniques developed in our laboratory along with conventional stopped-flow systems, we are able to follow biological reactions from microseconds to hours.

Representative Publications

(1) Hemoglobins from Unicellular Organisms

1. “A Novel Inter-subunit Communication Mechanism in a Truncated Hemoglobin from Mycobacterium Tuberculosis”
     Syun-Ru Yeh, J. Phys. Chem. B., 108, 1478-1484, 2004. [PDF]
2. “NO Binding Induced Conformational Changes in a Truncated Hemoglobin from M. Tuberculosis” 
    Masahiro Mukai, Yannick Ouellet, Hugues Ouellet, Michel Guertin & Syun-Ru Yeh
    Biochemisty, 43, 2764-70, 2004. [PDF]
3. “The Absence of Proximal Strain in the Truncated Hemoglobins from Mycobacterium Tuberculosis”
    Uri Samuni, Yannick Ouellet, Michel Guertin, Joel M. Friedman & Syun-Ru Yeh
    J. Am. Chem. Soc.,126, 2682-2683, 2004. [PDF]
4. “Unique ligand-protein interactions in a new truncated hemoglobin from Mycobacterium tuberculosis” 
    Masahiro Mukai, Pierre-Yves Savard, Hugues Ouellet, Michel Guertin & Syun-Ru Yeh, Biochemistry, 41,   
    3897-3905, 2002. [PDF]
5. "Flavohemoglobin: A Globin with A Peroxidase-Like Catalytic Site" 
    Masahiro Mukai, Catherine E. Mills, Robert K. Poole & Syun-Ru Yeh, J. Biol. Chem., 276, 7272-7277, 2001. [PDF]
6. "A cooperative oxygen binding hemoglobin from Mycobacterium tuberculosis: stabilization of heme ligands by a 
    distal tyrosine residue" 
    Syun-Ru Yeh, Manon Couture, Yannick Ouellet, Michel Guertin and Denis L. Rousseau, J. Biol. Chem., 
    1679-1684, 2000. [PDF]
7. "A cooperative oxygen binding hemoglobin from Mycobacterium tuberculosis" 
    Manon Couture, Syun-Ru Yeh, Beatrice A. Wittenberg, Jonathan B. Wittenberg, Yannick Ouellet, Denis L. 
    Rousseau & Michel Guertin, Proc. Natl. Acad. Sci. U. S. A., 96, 11223-11228, 1999. [PDF]

(2) Ultra-fast Kinetics in Protein Folding Reactions

1. “Modulation of the Folding Energy Landscape of Cytochrome c with Salt”
    Shi Zhong, Denis L. Rousseau and Syun-Ru Yeh, J. Am. Chem. Soc. 126, 13934-5, 2004. [PDF]
2. “Hierarchical Folding of Intestinal Fatty Acid Binding Protein”
    Syun-Ru Yeh, Ira J. Ropson, and Denis L. Rousseau, Biochemistry, 2001, 40, 4205-10, 2001. [PDF]
3. “Hierarchical Folding of Cytochrome c” 
    Syun-Ru Yeh and Denis L. Rousseau, Nature Struct. Biol. 7, 443-445, 2000. [PDF]  
4. "Submillisecond Unfolding Kinetics of Apomyoglobin and its pH 4 Intermediate" 
    Marc Jamin, Syun-Ru Yeh, Denis Rousseau and Robert L. Baldwin, J. Mol. Biol. 292, 731-740, 1999. [PDF]
5. "Cytochrome c Folding and Unfolding: A Biphasic Mechanism"
    Syun-Ru Yeh, Sanghwa Han and Denis L. Rousseau, Accounts of Chemical Research, 31, 727-736, 1998. [PDF]

(3) Others

1.“Heme distortion modulated by ligand-protein interactions in inducible nitric-oxide synthase”
    Li D, Stuehr DJ, Yeh SR, Rousseau DL., J Biol Chem. 279, 26489-99, 2004 [PDF]
2. “Modulation of the Electron Redistribution in Mixed-Valence Cytochrome c Oxidase by Protein Conformational   
    Changes”
    Hong Ji, Syun-Ru Yeh and Denis Rousseau , J. Biol. Chem., 279, 9392-9, 2004. [PDF]
2. “The heme environment of recombinant human indoleamine 2,3 dioxygenase: structural properties and 
    substrate-ligand interactions” 
    Andrew C. Terentis, Shane R. Thomas, Osamu Takikawa, Tamantha K. Littlejohn, Roger J. W. Truscott, Robert S. 
    Armstrong, Syun-Ru Yeh & Roland Stocker. J. Biol. Chem. 277, 15788-94, 2002. [PDF]
3. "Light-Modulated Electrokinetic Assembly of Planar Colloidal Arrays" 
    Syun-Ru Yeh, Michael Seul and Boris I. Shraiman, Nature, 386, 57-59, 1997.
4. “Applications of Photothermal Beam Deflection Calorimetry to Organic Photochemistry“
    Syun-Ru Yeh & Daniel E. Falvey,  J. Photochem. Photobiol., A: Chem., 87, 13-21, 1995.  [PDF]

Full List of Publications

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