Eileen K. Jaffe, PhD

Eileen Jaffe, PhD


Adjunct Professor, Department of Medical Genetics and Molecular Biochemistry, Lewis Katz School of Medicine, Temple University

Adjunct Professor, Department of Biochemistry and Molecular Biology, Drexel University College of Medicine

Research Program

Figure 1 The structure of PAH.
Figure 1 The structure of PAH. (a) The annotated domain structure of mammalian PAH. (b) The 2.9 Å PAH crystal structure in orthogonal views, colored as in part a, subunit A is shown in ribbons; subunit B is as a C-alpha trace; subunit C is in sticks; and subunit D is in transparent spheres. In cyan the subunits are labeled near the catalytic domain (top); in red they are labeled near the regulatory domain (bottom). The dotted black circle illustrates the autoregulatory domain partially occluding the enzyme active site (iron, in orange sphere). (c) Comparison of the subunit structures of full length PAH and those of the composite homology model; the subunit overlay aligns residues 144-410. The four subunits of the full length PAH structure (the diagonal pairs of subunits are illustrated using either black or white) are aligned with the two subunits of 2PAH (cyan) and the one subunit of 1PHZ (orange). The catalytic domain is in spheres, the regulatory domain is in ribbons, and the multimerization domain is as a C-alpha trace. The arrow denotes where the ACT domain and one helix of 2PAH conflict.
A structural roll of the dice
Morpheeins challenge a protein-folding paradigm
An unusual phylogenetic variation in the active site and allosteric metal ions of PBGS
The equilibrium of morpheein forms observed for human PBGS
Three models for allosteric regulation
Targeting morpheeins for drug design or discovery


Education and Training

Educational Background

  • Postdoctoral, Chemistry/Enzymology, Harvard University, 1979-1981
  • PhD, Biochemistry, University of Pennsylvania, 1979
  • BS, Chemistry, State University New York, Cortland, 1975


  • American Chemical Society 1975 - present
  • American Society for Biochemistry and Molecular Biology, 1986 - present
  • AAAS membership 1979 - present
  • Association for Women in Science 1982 - present
  • Sigma Xi 1979 - present
  • UPENN Biomedical Graduate Studies Advisory Board, 1992-1996Referee Panel X6A National Synchrotron Light Source, 2002-date
  • Advisory Board, Partnership for Cancer Research Education, FCCC, 1998 - 2006
  • Dean of Arts & Sciences Advisory Board, SUNY Cortland, 1999-2004
  • NIH Physiological Chemistry Study Section, 1997-2001

Honors & Awards

  • Elizabeth Bingham Award, AWIS-PHL, 2006
  • Academic Hall of Fame Inaugural Inductee, State University New York, Cortland, 2006
Research Profile

Research Program

Research Interests

Quaternary structure dynamics and the control of protein function

  • Morpheein model for protein allostery, for which the prototype is porphobilinogen synthase
  • Allosteric regulation of phenylalanine hydroxylase, a putative morpheein
  • Multimer-specific surface cavities as targets for the discovery of allosteric modulators (e.g. drugs)

Lab Overview

The Jaffe Laboratory studies protein structure-function relationships using both biochemical and biophysical approaches. We are focused on the roles of protein quaternary structure dynamics in the control of protein function. This follows our discovery that multimeric proteins can come apart, the dissociated units can change conformation, and these altered conformations can come back together differently to form a structurally and functionally distinct assembly.

Unlike amyloid, the changes in subunit structure are subtle, such as a hinge movement between folded domains, the oligomeric stoichiometry is finite, and the process is freely reversible. This structural dynamic can be the basis for allosteric regulation of protein function (the morpheein model of protein allostery). Disregulation of the equilibrium of assemblies is responsible for some human disease. Designed regulation of the equilibrium of assemblies provides a basis for allosteric drug discovery. The now well-established structural dynamic was originally unexpected, but new examples are being discovered regularly, as in the Ebola virus VP40 protein (E. Ollmann-Saphire, Scripps Institute). Although we coined the term morpheein to describe proteins that could reversibly dissociate, change conformation and assemble differently with finite stoichiometry, the term "transformers" has also been used. What we have learned from the prototype morpheein, porphobilinogen synthase, allows us to mine the literature and protein structure databases in search of other proteins that function as morpheeins. A family of putative morpheeins includes many drug targets, including cancer chemotherapeutic targets. The putative morpheein currently under most active investigation in the laboratory is phenylalanine hydroxylase, where the dysregulation of the interchange between various multimers is proposed to account for phenylketonuria in some patients.

Lab Staff

Michael Riis Hansen, PhD

Research Associate

Room: R452

Emily Arturo, BS

Graduate Student

Room: R452

Elias Borne, BA

Sci Tech I

Room: R452

Selected Publications

Simulations of the regulatory ACT domain of human phenylalanine hydroxylase (PAH) unveil its mechanism of phenylalanine binding. Ge Y, Borne E, Stewart S, Hansen MR, Arturo EC, Jaffe EK, Voelz VA. J Biol Chem. 2018, 293(51):19532-19543.  PMC6314134 PubMed

Biophysical characterization of full-length human phenylalanine hydroxylase provides a deeper understanding of its quaternary structure equilibrium, Arturo EC, Gupta K, Hansen MR, Borne E, Jaffe EK. J Biol Chem. 2019, 294(26):10131-10145. PMID: 31076506

New protein structures provide an updated understanding of phenylketonuria. Jaffe EK. Mol Genet Metab. 2017 Aug;121(4):289-296. doi: 10.1016/j.ymgme.2017.06.005. Epub 2017 Jun 15. Review. PMID: 28645531 PubMed

The Remarkable Character of Porphobilinogen Synthase. Jaffe EK. Acc Chem Res. 2016 Nov 15;49(11):2509-2517. Epub 2016 Oct 26. PubMed

First structure of full-length mammalian phenylalanine hydroxylase reveals the architecture of an autoinhibited tetramer. Arturo EC, Gupta K, Héroux A, Stith L, Cross PJ, Parker EJ, Loll PJ, Jaffe EK. Proc Natl Acad Sci U S A. 2016 Mar 1;113(9):2394-9. doi: 10.1073/pnas.1516967113. Epub 2016 Feb 16. PubMed

Ramirez UD, Nikonova AS, Liu H, Pecherskaya A, Lawrence SH, Serebriiskii IG, et al. Compounds identified by virtual docking to a tetrameric EGFR extracellular domain can modulate Grb2 internalization. BMC cancer. 2015;15:436. PMC4451962. PubMed

Lawrence SH, Selwood T, Jaffe EK. Environmental contaminants perturb fragile protein assemblies and inhibit normal protein function. Curr Chem Biol. 2013;7 PMC4102012. PubMed

Jaffe EK, Stith L, Lawrence SH, Andrake M, Dunbrack RL, Jr. A new model for allosteric regulation of phenylalanine hydroxylase: implications for disease and therapeutics. Arch Biochem Biophys. 2013;530(2):73-82. PMC3580015. PubMed

Jaffe EK. Impact of quaternary structure dynamics on allosteric drug discovery. Curr Top Med Chem. 2013;13(1):55-63. PMC3631351. PubMed

Selwood T, Jaffe EK. Dynamic dissociating homo-oligomers and the control of protein function. Arch Biochem Biophys. 2012;519(2):131-43. PMC3298769. PubMed

Lawrence SH, Selwood T, Jaffe EK. Diverse clinical compounds alter the quaternary structure and inhibit the activity of an essential enzyme. ChemMedChem. 2011;6(6):1067-73. PMC3236527. PubMed

Jaffe EK. Morpheeins - a New Pathway for Allosteric Drug Discovery. Open Conf Proc J. 2010;1:1-6. PMC3107518. PubMed

Additional Publications


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