Faculty Summaries
Eileen K. Jaffe, PhD
Eileen K. Jaffe, PhD
Professor
  • Adjunct Professor, Bichemistry, University of Pennsylvania School of Dental Medicine
  • Adjunct Professor, Biochemistry & Molecular Biology, Drexel University College of Medicine
  • Adjunct Professor of Biochemistry, Temple University School of Medicine
Eileen.Jaffe@fccc.edu
Office Phone: 215 728-3695
Lab Phone: 215 728-5268
Fax: 215 728-2412
Office: R455
Lab: R452
The Role of Protein Quaternary Structure in the Control of Function

The Jaffe laboratory studies protein structure-function relationships using both biochemical and biophysical approaches. We have recently become focused on the roles of protein quaternary structure dynamics in the control of protein function. This follows our discovery that at least one homo-oligomeric protein can dissociate, the dissociated units can change conformation, and these altered conformations support association to a structurally and functionally distinct oligomeric assembly. Unlike the prion phenomenon, our characterized changes in subunit structure are subtle, the oligomeric stoichiometry is finite, and the process is freely reversible. We have associated this structural dynamic with allosteric regulation of protein function, with human disease, and with new opportunities for allosteric drug discovery. The now well established structural dynamic was originally unexpected and we were reticent to accept its validity. However, realizing the novelty of this discovery, we coined the term morpheein to describe proteins that could reversibly dissociate, change conformation, and assemble differently with finite stoichiometry. What we have learned from the prototype morpheein allows us to mine the literature and protein structure databases in search of other proteins that function as morpheeins. We have identified a family of putative morpheeins, many of which can be approached as drug targets, including cancer chemotherapeutic targets.

Description of research projects
Selected Publications
  1. Jaffe, E.K., Stith, L., Lawrence, S.H., Andrake, M., Dunbrack, R.L., (2013) A new model for allosteric regulation of phenylalanine hydroxylase: Implications for disease and therapeutics. Arch Biochem Biophys 530 (2):73-82. Pubmed
  2. Jaffe, E.K. (2013) Impact of Quaternary Structure Dynamics on Allosteric Drug Discovery, Current Topics in Medicinal Chemistry  13 (1): 55-63. PubMed
  3. Selwood T, Jaffe EK. Dynamic dissociating homo-oligomers and the control of protein function. Arch Biochem Biophys. 2012 Mar 15;519(2):131-43. PubMed
  4. Jaffe EK, Lawrence SH. Allostery and the dynamic multimerization of porphobilinogen synthase. Arch Biochem Biophys. 2012;519:144-53. PubMed
  5. Lawrence SH, Ramirez UD, Tang L, Fazliyez F, Kundrat L, Markham GD, Jaffe EK. Shape shifting leads to small-molecule allosteric drug discovery. Chem Biol. 2008;15:586-96. PubMed
  6. Jaffe EK, Stith L. ALAD Porphyria Is a Conformational Disease. Am J Hum Genet. 2007 80:329-37. PubMed
  7. Jaffe EK. Morpheeins - a new structural paradigm for allosteric regulation. Trends Biochem Sci. 2005;30:490-7. PubMed
  8. Breinig, S., Kervinen, J., Stith, L., Fairman, R., Wasson, A.S., Wlodawer, A., Zdanov, A., Jaffe, E.K.  Control of tetrapyrrole biosynthesis by alternate quaternary forms of porphobilinogen synthase.  Nat. Struct. Biol. 10:757-763, 2003. PubMed
All publications