James Manning

James ManningProfessor
Protein Structure and Function

Department of Biology
Northeastern University
420C Mugar Life Sciences
360 Huntington Avenue
Boston, MA 02115

Academic Education

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


  • Professor of Biochemistry, Northeastern University (1996 – Present)
  • Adjunct Professor, The Rockefeller University (1996 – Present)
  • Associate Professor of Biochemistry (tenured), The Rockefeller University (1978– 1995)
  • Head of Biochemistry Laboratory, The Rockefeller University (1988 – 1995)
  • Adjunct Associate Professor of Biochemistry, Cornell University Medical College (1975 – 1995)
  • Associate Professor of Biochemistry (untenured), The Rockefeller University (1972 – 1977)
  • Assistant Professor of Biochemistry, The Rockefeller University (1969-1972)
  • Research Associate, The Rockefeller University (1967 – 1969)
  • National Science Foundation Postdoctoral Fellow, University of Rome, Italy (1966 – 1967)
  • USPHS Pre-doctoral Fellow, Tufts University (1960 – 1966)

Other Professional Activities

  • Editorial Board, Protein Science (2005 – Present)
  • National Institutes of Health Parent Committee (1992-Present)
  • National Institutes of Health ad hoc Study Sections (1973-Present)
  • NIH Merit Award (1987-1997)
  • Journal of Biological Chemistry, Editorial Board (1979 -1984 and 1990 – 1995)
  • The New England Enzyme Center, Scientific Advisory Committee (1975-1986)
  • National Science Foundation, Postdoctoral Fellowship Evaluation Panel (1977-1979), Chairman (1979)
  • American Society of Biological Chemists, Membership Committee, Chairman (1977-1979)
  • American Heart Association, Grants Review Committee (1976-1978)

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.

Teaching Activities

I teach BIOL2323, Biochemistry and BIOL7303, Structural Biology. Biochemistry, BIOL2323, is an undergraduate-level course that stresses an understanding of the basic functions of biological molecules with particular emphasis on their chemical reactivities and inter-relationships. Specifically, proteins (normal and abnormal) are studied as well as DNA/RNA, genes, enzymes (kinetics and regulation), carbohydrates, bioinergetics, amino acids (structural and metabolism), protein biosynthesis, fatty acids and lipids, steroids, hormones, and photosynthesis.

Structural Biology, BIOL7303, describes examples where the function can be explained by a structure, as in normal stable proteins. Misfolded proteins, where a structure is partially solved, is also discussed. The normal stable proteins that are discussed: myoglobin/hemoglobin, the oxygen carriers, the chaperonin system – for protein folding, the ribosome – the protein biosynthesis factory, the nucleosome, the DNA-histone complex, the potassium channel – involved in nerve conductance. Mis-folded proteins is an emerging field where structures are less certain than with stable proteins. Systems that are covered include amyloid, prions, and ALS (amyotrophic lateral sclerosis, Lou Gherig’s disease).


  • James M.Manning, Anthony M. Popowicz, Julio C. Padovan, Brian T. Chait, and Lois R. Manning. Intrinsic Regulation of Hemoglobin Expression by Variable Subunit Interface Strengths. FEBS Journal, Vol.279, 361-369 (2012).
  • Lois R. Manning, Anthony M. Popowicz, Julio Padovan, Brian T. Chait, J. Eric Russell, and James M. Manning. Developmental Expression of Human Hemoglobins Mediated by Maturation of Their Subunit Interfaces. Protein Science: 19, 1595-1599 (2010).
  • Lois R. Manning, J. Eric Russell, Anthony M. Popowicz, Robert S. Manning, Julio C. Padovan, and James M. Manning. Energetic Differences at the Subunit Interfaces of Normal Human Hemoglobins Correlate with Their Developmental Profile. Biochemistry, 48: 7568-7574 (2009).
  • Lois R. Manning, J. Eric Russell, Julio C. Padovan, Brian T. Chait, Anthony Popowicz, Robert S. Manning, and James M. Manning. Human embryonic, fetal, and adult hemoglobins have different subunit interface strengths. Correlation withlifespan in the red cell. Protein Science, 16:1641 – 1658 (2007).
  • M. Ashiuchi, T. Yagami, R.J. Willey, J.C. Padovan, B.T. Chait, A. Popowicz, L.R. Manning, and J.M. Manning. N-Terminal Acetylation and Protonation of Individual Hemoglobin Subunits. Protein Science, 14:1458 – 1471 (2005).
  • A.Geva, J.J. Clark, Y.Zhang, A. Popowicz, J.M. Manning, and E.J. Neufeld. Hemoglobin Jamaica Plain–A Dominant Sickling Hemoglobin with Reduced Oxygen Affinity. New England Journal of Medicine, 315, 40-46 (2004).
  • Y. Zhang, L.R. Manning, J.Falcone, O.Platt, and J.M. Manning. Human Erythrocyte Membrane Band 3 Protein Influences Hemoglobin Cooperativity. Possible Effect on Oxygen Transport. J.Biol.Chem. 278,39565-39571 (2003).
  • X. Li, R.W. Briehl, R.M. Bookchin, R. Josephs, B. Wei, J.M. Manning, and F.A. Ferrone. Sickle Hemoglobin Polymer Stability Probed by Triple and Quadruple Mutant Hybrids. J. Biol. Chem. 277, 13479-13487 (2002).
  • T. Yagami, B.T. Ballard, J.C. Padovan, B.T. Chait, A.M. Popowicz, and J.M. Manning. N-Terminal Contributions of the y-Subunit of Fetal Hemoglobin to its Tetramer Strength. Remote Effects of Subunit Contacts. Protein Science. 11, 27-35 (2002).
  • K. Kishimoto and J.M. Manning. Adherence of Vancomycin to Proteins. J. Protein Chem. 20, 455-461 (2001).
  • L.R. Manning and J.M. Manning. The Acetylation State of Human Fetal Hemoglobin Modulates the Strength of Its Subunits Interactions: Long-Range Effects and Implications for Histone Interactions in the Nucleosome. Biochemistry. 40, 1635-1639 (2001).
  • K. Inagaki, J. Inagaki, A. Dumoulin, J.C. Padovan, B.T. Chait, A. Popowicz, L.R. Manning, and J.M. Manning. Expression and Properties of Recombinant HbA2(a2d2) and Hybrids Containing Delta-Beta Sequences. J. Prot. Chem. 19, 647-660 (2000).