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

Peer Reviewed Publications

  • Lawrence, S.H., Selwood, T., Jaffe, E.K. (2012) Environmental contaminants perturb fragile protein assemblies and inhibit normal protein function. Current Chemical Biology 7(2), (in press). PMC Journal in Process.
  • Jaffe, E.K. (2013) Impact of Quaternary Structure Dynamics on Allosteric Drug Discovery, Current Topics in Medicinal Chemistry  13 (1): 55-63. PMC Journal in Process.
  • 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. PMC3580015 PubMed  
  • Velvadapu V, McDonnell ME, Jaffe EK, Reitz AB. Facile Synthesis of Mutagen X (MX): 3-Chloro-4-(dichloromethyl)-5-hydroxy-5H-furan-2-one. Tetrahedron Lett. 2012 Jun 20;53(25):3144-3146. PubMed PMID: 22822274; PubMed Central PMCID: PMC3398704. PubMed
  • 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
  • Jaffe EK, Lawrence SH. Allostery and the dynamic multimerization of porphobilinogen synthase. Arch Biochem Biophys. 2012;519:144-53. PubMed
  • Jaffe EK, Lawrence SH. The morpheein model of allostery: Evaluating proteins as potential morpheeins. A chapter in Methods in Molecular Biology - Monitoring Allosteric Function. Methods Mol Biol. 2012;796:217-31. PubMed
  • Lawrence SH, Selwood T, Jaffe EK. Diverse clinical compounds alter the quaternary structure and inhibit the activity of an essential enzyme. ChemMedChem. 2011 Jun 6;6(6):1067-73. doi: 10.1002/cmdc.201100009. PubMed
  • Jaffe EK, Shanmugan D, Gardberg A, Dieterich M, Banumathi S, Stewart LJ, Myler PJ, Roos DS. Crystal structure of Toxoplasma gondii porphobilinogen synthase: Insight on octameric structure and porphobilinogen formation. J Biol Chem. 2011 Mar 7. PubMed
  • Ramirez UD, Myachina F, Stith L, Jaffe EK. Docking to large allosteric binding sites on protein surfaces. Adv Exp Med Biol. 2010;680:481-8. PubMed
  • Jaffe EK. Morpheeins, a new pathway for allosteric drug discovery. Open Conf Proc J. 2010;1:1-6. PubMed
  • Reitz AB, Ramirez UD, Stith L, Du Y, Smith GR, Jaffe EK. Pseudomonas aeruginosa porphobilinogen synthase assembly state regulators: hit discovery and initial SAR studies. ARKIVOC. 2010 Jun;2010:175-188. PubMed
  • Shanmugam D, Wu B, Ramirez U, Jaffe EK, Roos DS. Plastid-associated porphobilinogen synthase from Toxoplasma gondii: kinetic and structural properties validate therapeutic potential. J Biol Chem. 2010 Jul 16;285(29):22122-31. PubMed
  • Lawrence SH, Ramirez UD, Selwood T, Stith L, Jaffe EK. Allosteric inhibition of human porphobilinogen synthase. J Biol Chem. 2009 Dec 18;284(51):35807-17. PubMed
  • Kokona B, Rigotti DJ, Wasson AS et al. Probing the Oligomeric Assemblies of Pea Porphobilinogen Synthase by Analytical Ultracentrifugation. Biochemistry. 2008;47(40):10649-56. PubMed.
  • Lawrence SH, Jaffe EK. Expanding the concepts in protein-structure-function relationships and enzyme kinetics: Teaching using morpheeins. Biochem Mol Biol Educ. 2008;36(4):274-83. PubMed.
  • Lawrence SH, Ramirez UD, Tang L et al. Shape shifting leads to small-molecule allosteric drug discovery. Chem Biol. 2008c;15(6):586-96. PubMed.
  • Selwood T, Tang L, Lawrence SH et al. Kinetics and thermodynamics of the interchange of the morpheein forms of human porphobilinogen synthase. Biochemistry. 2008;47(10):3245-57. PubMed.
  • Jaffe EK, Stith L. ALAD porphyria is a conformational disease. Am J Hum Genet. 2007;80(2):329-37. PubMed.
  • Shenker BJ, Dlakic M, Walker LP et al. A Novel Mode of Action for a Microbial-Derived Immunotoxin: The Cytolethal Distending Toxin Subunit B Exhibits Phosphatidylinositol (3,4,5)-Trisphosphate Phosphatase Activity. J Immunol. 2007;178(8):5099-108. PubMed.
  • Akagi R, Kato N, Inoue R et al. delta-Aminolevulinate dehydratase (ALAD) porphyria: the first case in North America with two novel ALAD mutations. Mol Genet Metab. 2006;87(4):329-36. PubMed.
  • Tang L, Breinig S, Stith L et al. Single amino acid mutations alter the distribution of human porphobilinogen synthase quaternary structure isoforms (morpheeins). J Biol Chem. 2006;281(10):6682-90. PubMed.
  • Cheng JD, Valianou M, Canutescu AA et al. Abrogation of fibroblast activation protein enzymatic activity attenuates tumor growth. Mol Cancer Ther. 2005;4(3):351-60. PubMed.
  • Jaffe EK. Morpheeins - a new structural paradigm for allosteric regulation. Trends Biochem Sci. 2005;30(9):490-7. PubMed.
  • Tang L, Stith L, Jaffe EK. Substrate-induced interconversion of protein quaternary structure isoforms. J Biol Chem. 2005;280(16):15786-93. PubMed.
  • Bollivar DW, Clauson C, Lighthall R et al. Rhodobacter capsulatus porphobilinogen synthase, a high activity metal ion independent hexamer. BMC Biochem. 2004;5:No pp given. PubMed.
  • Jaffe EK. The porphobilinogen synthase catalyzed reaction mechanism. Bioorg Chem. 2004;32(5):316-25. PubMed.
  • Breinig S, Kervinen J, Stith L et al. Control of tetrapyrrole biosynthesis by alternate quaternary forms of porphobilinogen synthase. Nat Struct Biol. 2003;10(9):757-63. PubMed.
  • Jaffe EK. Investigations on the metal switch region of human porphobilinogen synthase. JBIC, J Biol Inorg Chem. 2003a;8(1-2):176-84. PubMed.
  • Jaffe EK. An unusual phylogenetic variation in the metal ion binding sites of porphobilinogen synthase. Chem Biol. 2003;10(1):25-34. PubMed.
  • Kundrat L, Martins J, Stith L et al. A structural basis for half-of-the-sites metal binding revealed in Drosophila melanogaster porphobilinogen synthase. J Biol Chem. 2003;278(33):31325-30. PubMed.
  • Jaffe EK, Kervinen J, Martins J et al. Species-specific inhibition of porphobilinogen synthase by 4-oxosebacic acid. J Biol Chem. 2002;277(22):19792-9. PubMed.
  • Jaffe EK, Martins J, Li J et al. The molecular mechanism of lead inhibition of human porphobilinogen synthase. J Biol Chem. 2001;276(2):1531-7. PubMed.
  • Kervinen J, Jaffe EK, Stauffer F et al. Mechanistic basis for suicide inactivation of porphobilinogen synthase by 4,7-dioxosebacic acid, an inhibitor that shows dramatic species selectivity. Biochemistry. 2001;40(28):8227-36. PubMed.
  • Mitchell LW, Volin M, Martins J et al. Mechanistic implications of mutations to the active site lysine of porphobilinogen synthase. J Biol Chem. 2001;276(2):1538-44. PubMed.
  • Jaffe EK. The porphobilinogen synthase family of metalloenzymes. Acta Crystallogr D Biol Crystallogr. 2000;56(Pt 2):115-28. PubMed.
  • Jaffe EK, Volin M, Bronson-Mullins CR et al. An artificial gene for human porphobilinogen synthase allows comparison of an allelic variation implicated in susceptibility to lead poisoning. J Biol Chem. 2000;275(4):2619-26. PubMed.
  • Kervinen J, Dunbrack RL, Jr., Litwin S et al. Porphobilinogen synthase from pea: expression from an artificial gene, kinetic characterization, and novel implications for subunit interactions. Biochemistry. 2000;39(30):9018-29. PubMed.
  • Frankenberg N, Jahn D, Jaffe EK. Pseudomonas aeruginosa Contains a Novel Type V Porphobilinogen Synthase with No Required Catalytic Metal Ions. Biochemistry. 1999;38(42):13976-82. PubMed.
  • Shimoni-Livny L, Carrell HL, Wagner T et al. Crystallization and preliminary x-ray diffraction studies of E. coli porphobilinogen synthase and its heavy-atom derivatives. Acta Crystallogr, Sect. D: Biol Crystallogr. 1998;D54(3):438-40. PubMed.
  • Clarkson J, Jaffe EK, Petrovich RM et al. Opportunities for Probing the Structure and Mechanism of Porphobilinogen Synthase by Raman Spectroscopy. J Am Chem Soc. 1997;119(47):11556-7.
  • Petrovich RM, Jaffe EK. Magnetic Resonance Studies on the Active Site and Metal Centers of Bradyrhizobium japonicum Porphobilinogen Synthase. Biochemistry. 1997;36(43):13421-7. PubMed.
  • Carrell HL, Glusker JP, Shimoni L et al. Crystallization and preliminary x-ray diffraction studies of 5-chlorolevulinate-modified bovine porphobilinogen synthase and the PbII-complexed enzyme. Acta Crystallogr., Sect. D: Biol Crystallogr. 1996;D52(2):419-21. PubMed
  • Petrovich RM, Litwin S, Jaffe EK. Bradyrhizobium japonicum porphobilinogen synthase uses two Mg(II) and monovalent cations. J Biol Chem. 1996;271(15):8692-9. PubMed.
  • Jaffe EK. Porphobilinogen synthase, the first source of heme's asymmetry. J Bioenerg Biomembr. 1995;27(2):169-79. PubMed.
  • Jaffe EK, Ali S, Mitchell LW et al. Characterization of the Role of the Stimulatory Magnesium of Escherichia coli Porphobilinogen Synthase. Biochemistry 1995;34(1):244-51. PubMed.
  • Jaffe EK, Petrovich RM, Volin M. 5-Chlorolevulinate interactions with Bradyrhizobium japonicum porphobilinogen synthase. Bioorg Chem. 1995;23(4):450-9.
  • Mitchell LW, Volin M, Jaffe EK. The phylogenetically conserved histidines of Escherichia coli porphobilinogen synthase are not required for catalysis. J Biol Chem. 1995;270 (41):24054-9. PubMed
  • Jaffe EK, Volin M, Myers CB et al. 5-Chloro[1,4-13C]levulinic acid modification of mammalian and bacterial porphobilinogen synthase suggests an active site containing two Zn(II). Biochemistry. 1994;33(38):11554-62. PubMed.
  • Jaffe EK. Predicting the Zn(II) ligands in metalloproteins: case study, porphobilinogen synthase. Comments Inorg. Chem. 1993;15(2):67-92.
  • Markham GD, Myers CB, Harris KA, Jr. et al. Spatial proximity and sequence localization of the reactive sulfhydryls of prophobilinogen synthase. Protein Sci. 1993;2(1):71-9. PubMed.
  • Mitchell LW, Jaffe EK. Porphobilinogen synthase from Escherichia coli is a zinc(II) metalloenzyme stimulated by magnesium(II). Arch Biochem. Biophys. 1993;300(1):169-77. PubMed.
  • Rajagopalan JS, Jaffe EK. Microbial production and NMR characterization of [2,6,9-13C]chorismate and [1,3,5,8-13C]chorismate. Bioorg. Med. Chem. Lett. 1993; 3 (7):1453-6.
  • Rajagopalan JS, Taylor KM, Jaffe EK. Carbon-13 NMR studies of the enzyme-product complex of Bacillus subtilis chorismate mutase. Biochemistry 1993b; 32 (15):3965-72. PubMed.
  • Afshar C, Jaffe EK, Carrell HL et al. The molecular conformation of chorismic acid in the crystalline state. Bioorg Chem. 1992;20(4):323-33.
  • Jaffe EK, Abrams WR, Kaempfen HX et al. 5-Chlorolevulinate modification of porphobilinogen synthase identifies a potential role for the catalytic zinc. Biochemistry. 1992;31(7):2113-23. PubMed.
  • Rajagopalan JS, Chen LC, Jaffe EK. Preparation, carbon-13 NMR characterization, and enzymic transformation of [U-13C]chorismate to [U-13C]prephenate and [U-13C]hydroxyphenyl pyruvate. Bioorg Chem. 1992;20(2):115-23.
  • Jaffe EK, Bagla S, Michini PA. Reevaluation of a sensitive indicator of early lead exposure: measurement of porphobilinogen synthase in blood. Biol Trace Elem Res. 1991;28(3):223-31. PubMed.
  • Jaffe EK, Markham GD, Rajagopalan JS. 15N and 13C NMR studies of ligands bound to the 280,000-dalton protein porphobilinogen synthase elucidate the structures of enzyme-bound product and a Schiff base intermediate. Biochemistry. 1990;29 (36):8345-50. PubMed.
  • Jaffe EK, Rajagopalan JS. Nuclear magnetic resonance studies of 5-aminolevulinate demonstrate multiple forms in aqueous solution. Bioorg Chem. 1990;18(4):381-94.
  • Jaffe EK, Markham GD. Carbon-13 NMR studies of methylene and methine carbons of substrate bound to a 280,000-dalton protein, porphobilinogen synthase. Biochemistry. 1988;27(12):4475-81. PubMed.
  • Jaffe EK, Markham GD. Carbon-13 NMR studies of porphobilinogen synthase: observation of intermediates bound to a 280,000-dalton protein. Biochemistry. 1987;26(14):4258-64. PubMed.
  • Jaffe EK, Hanes D. Dissection of the early steps in the porphobilinogen synthase catalyzed reaction. Requirements for Schiff's base formation. J Biol Chem. 1986;261(20):9348-53. PubMed.
  • Jaffe EK, Salowe SP, Chen NT et al. Porphobilinogen synthase modification with methylmethanethiosulfonate. A protocol for the investigation of metalloproteins. J Biol Chem. 1984;259(8):5032-6. PubMed.
  • Addadi L, Jaffe EK, Knowles JR. Secondary tritium isotope effects as probes of the enzymic and nonenzymic conversion of chorismate to prephenate. Biochemistry. 1983;22(19):4494-501. PubMed.
  • Jaffe EK, Nick J, Cohn M. Reactivity and metal-dependent stereospecificity of the phosphorothioate analogs of ADP and ATP and reactivity of chromium(III)-ATP in the 3-phosphoglycerate kinase reaction. Structure of the metal nucleotide substrates. J Biol Chem. 1982;257(13):7650-6. PubMed.
  • Jaffe EK, Cohn M. Shift of the equilibrium constant of the 3-phosphoglycerate kinase reaction towards 1,3-bis-phosphoglycerate with adenosine 5'-O-(2-thiotriphosphate) (ATPbS) as substrate. J Biol Chem. 1980;255(8):3240-1.
  • PubMed.
  • Jaffe EK, Cohn M. Shift of the equilibrium constant of the 3-P-glycerate kinase reaction towards 1,3-bis-P-glycerate with adenosine 5'-O-(2-thiotriphosphate) (ATP beta S) as substrate. J Biol Chem. 1980;255(8):3240-1. PubMed.
  • Jaffe EK, Cohn M. Diastereomers of the nucleoside phosphorothioates as probes of the structure of the metal nucleotide substrates and of the nucleotide binding site of yeast hexokinase. J Biol Chem. 1979;254(21):10839-45. PubMed.
  • Jaffe EK, Cohn M. Phosphorus-31 nuclear magnetic resonance spectra of the thiophosphate analogs of adenine nucleotides; effects of pH and magnesium(2+) binding. Biochemistry. 1978;17(4):652-7.
  • PubMed.
  • Jaffe EK, Cohn M. 31P nuclear magnetic resonance spectra of the thiophosphate analogues of adenine nucleotides; effects of pH and Mg2+ binding. Biochemistry. 1978;17(4):652-7. PubMed.
  • Jaffe EK, Cohn M. Divalent cation-dependent stereospecificity of adenosine 5'-O-(2-thiotriphosphate) in the hexokinase and pyruvate kinase reactions. The absolute stereochemistry of the diastereoisomers of adenosine 5'-O-(2-thiotriphosphate). J Biol Chem. 1978;253(14):4823-5. PubMed.
  • Jaffe EK, Zipp AP. Spectroscopic and equilibrium studies of adduct formation between sulfoxides and bis(2,4-pentanedionato)oxovanadium(IV). Journal of Inorganic and Nuclear Chemistry. 1978;40 (5):839-41.
  • Owen CS, Jaffe EK, Wilson DF. Application of a superconducting susceptometer to biological samples. Rev Sci Instr. 1977;48:1541-4.
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Published Patents

  • Jaffe, E.K. Alternate morpheein forms of allosteric proteins as a target for the development of bioactive molecules.  U.S. Patent 8,153,410 B2, April 10, 2012.   
  • Jaffe EK.  Alternate morpheeins of allosteric proteins as a target for the development of bioactive molecules.  U.S. Patent Serial No. 12/106,498, Jan 4, 2011.
  • Jaffe EK.  Blood Lead Diagnostic Assay.  U.S. Patent No. 08/100,980, 1996.
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