James Manning

Degrees/Education

Ph.D., Biochemistry, Tufts University
B.S., Chemistry, Boston College

Area(s) of Expertise

Protein Structure and Function

Research Interests

Our goal is to further our understanding of proteins, especially those that have important biological functions. We employ both the classical methods of protein chemistry as well as the newer recombinant DNA technology.

Hemoglobin – A previously unrecognized function of normal human hemoglobins occurring during protein assembly is self-regulation of subunit pairings and their durations arising from the variable strengths of their subunit interactions. The subunit interface strengths of the normal embryonic, fetal, and adult human hemoglobins have not been considered to differ significantly. However, we found that the strengths, i.e., the free energies of the tetramer – dimer interfaces, contrary to previous reports, differ by 3 orders of magnitude and display an undulating profile similar to the transitions (“switches”) of various globin subunit types over time. The dimer interface strengths are also variable and correlate linearly with their developmental profile. Embryonic hemoglobin are the weakest; fetal hemoglobin is of intermediate strength, and adult hemoglobins are the strongest. The relative contributions of globin gene order and competition among subunits due to differences in their interface strengths were found to be complementary and establish a connection for genetics, thermodynamics, and development.

Acylpeptide Hydrolase – The biological role of this enzyme may be to remove the acetyl group together with the first amino acid of nascent polypeptide chains as a co-translational event during protein biosynthesis. The enzyme also acts on N-blocked bioactive peptides. We have recently identified the active site Serine and Histidine residues in the catalytic triad of this protease. Acylpeptide hydrolase belongs to the new class of proteases, the hydrolase-fold family.

Location

420C Mugar Life Sciences Building