E K Jaffe

Summary

Affiliation: Fox Chase Cancer Center
Country: USA

Publications

  1. ncbi request reprint The molecular mechanism of lead inhibition of human porphobilinogen synthase
    E K Jaffe
    Institute for Cancer Research, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA
    J Biol Chem 276:1531-7. 2001
  2. ncbi request reprint The porphobilinogen synthase catalyzed reaction mechanism
    Eileen K Jaffe
    Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111, USA
    Bioorg Chem 32:316-25. 2004
  3. ncbi request reprint An unusual phylogenetic variation in the metal ion binding sites of porphobilinogen synthase
    Eileen K Jaffe
    Institute for Cancer Research, Fox Chase Cancer Center, 7701 Burholme Avenue, Philadelphia, PA 19111, USA
    Chem Biol 10:25-34. 2003
  4. ncbi request reprint Investigations on the metal switch region of human porphobilinogen synthase
    Eileen K Jaffe
    Institute for Cancer Research, Fox Chase Cancer Center, 7701 Burholme Avenue, Philadelphia, PA 19111, USA
    J Biol Inorg Chem 8:176-84. 2003
  5. ncbi request reprint Species-specific inhibition of porphobilinogen synthase by 4-oxosebacic acid
    Eileen K Jaffe
    Institute for Cancer Research, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA
    J Biol Chem 277:19792-9. 2002
  6. ncbi request reprint Mechanistic basis for suicide inactivation of porphobilinogen synthase by 4,7-dioxosebacic acid, an inhibitor that shows dramatic species selectivity
    J Kervinen
    Institute for Cancer Research, Fox Chase Cancer Center, 7701 Burholme Avenue, Philadelphia, Pennsylvania 19111, USA
    Biochemistry 40:8227-36. 2001
  7. ncbi request reprint Mechanistic implications of mutations to the active site lysine of porphobilinogen synthase
    L W Mitchell
    Institute for Cancer Research, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA
    J Biol Chem 276:1538-44. 2001
  8. ncbi request reprint Characterization of the role of the stimulatory magnesium of Escherichia coli porphobilinogen synthase
    E K Jaffe
    Institute for Cancer Research, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111
    Biochemistry 34:244-51. 1995
  9. ncbi request reprint An artificial gene for human porphobilinogen synthase allows comparison of an allelic variation implicated in susceptibility to lead poisoning
    E K Jaffe
    Institute for Cancer Research, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA
    J Biol Chem 275:2619-26. 2000
  10. ncbi request reprint Control of tetrapyrrole biosynthesis by alternate quaternary forms of porphobilinogen synthase
    Sabine Breinig
    Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, Pennsylvania 19111 2497, USA
    Nat Struct Biol 10:757-63. 2003

Collaborators

Detail Information

Publications24

  1. ncbi request reprint The molecular mechanism of lead inhibition of human porphobilinogen synthase
    E K Jaffe
    Institute for Cancer Research, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA
    J Biol Chem 276:1531-7. 2001
    ..The data support a novel model where a high affinity lead site is a hybrid of the ZnA and ZnB sites. We propose that the lone electron pair of Pb(II) precludes Pb(II) to function in PBGS catalysis...
  2. ncbi request reprint The porphobilinogen synthase catalyzed reaction mechanism
    Eileen K Jaffe
    Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111, USA
    Bioorg Chem 32:316-25. 2004
    ..The reaction appears to stall at a covalently bound almost-product intermediate that is poised for breakdown to product upon binding of a substrate molecule to an adjacent active site and a subsequent conformational change...
  3. ncbi request reprint An unusual phylogenetic variation in the metal ion binding sites of porphobilinogen synthase
    Eileen K Jaffe
    Institute for Cancer Research, Fox Chase Cancer Center, 7701 Burholme Avenue, Philadelphia, PA 19111, USA
    Chem Biol 10:25-34. 2003
    ..The phylogenetic distribution of PBGS metal ion utilization suggests that the primordial PBGS required zinc and supports a hypothesis that the loss of the zinc site was concurrent with the advent of oxygenic photosynthesis...
  4. ncbi request reprint Investigations on the metal switch region of human porphobilinogen synthase
    Eileen K Jaffe
    Institute for Cancer Research, Fox Chase Cancer Center, 7701 Burholme Avenue, Philadelphia, PA 19111, USA
    J Biol Inorg Chem 8:176-84. 2003
    ..The R221K mutation was inserted into wild type and chimeric human PBGS and found to further reduce the activity of both, illustrating the subtle nature of the role of this residue...
  5. ncbi request reprint Species-specific inhibition of porphobilinogen synthase by 4-oxosebacic acid
    Eileen K Jaffe
    Institute for Cancer Research, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA
    J Biol Chem 277:19792-9. 2002
    ..A comparison of these with other PBGS structures identifies highly conserved active site water molecules, which are isolated from bulk solvent and implicated as proton acceptors in the PBGS-catalyzed reaction...
  6. ncbi request reprint Mechanistic basis for suicide inactivation of porphobilinogen synthase by 4,7-dioxosebacic acid, an inhibitor that shows dramatic species selectivity
    J Kervinen
    Institute for Cancer Research, Fox Chase Cancer Center, 7701 Burholme Avenue, Philadelphia, Pennsylvania 19111, USA
    Biochemistry 40:8227-36. 2001
    ..coli numbering). This is the first structure to show inhibitor binding at the second of two substrate-binding sites...
  7. ncbi request reprint Mechanistic implications of mutations to the active site lysine of porphobilinogen synthase
    L W Mitchell
    Institute for Cancer Research, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA
    J Biol Chem 276:1538-44. 2001
    ..Thus, formation of the lysine to ALA Schiff base is not required to initiate the asymmetry that results in half-site reactivity...
  8. ncbi request reprint Characterization of the role of the stimulatory magnesium of Escherichia coli porphobilinogen synthase
    E K Jaffe
    Institute for Cancer Research, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111
    Biochemistry 34:244-51. 1995
    ..The addition of unlabeled or 1-13C-labeled ALA does not significantly affect the Mn(II) EPR spectra.(ABSTRACT TRUNCATED AT 250 WORDS)..
  9. ncbi request reprint An artificial gene for human porphobilinogen synthase allows comparison of an allelic variation implicated in susceptibility to lead poisoning
    E K Jaffe
    Institute for Cancer Research, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA
    J Biol Chem 275:2619-26. 2000
    ..However, there was no differential displacement of Zn(II) by Pb(II) between K59 and N59, and simple Pb(II) inhibition studies revealed no allelic difference...
  10. ncbi request reprint Control of tetrapyrrole biosynthesis by alternate quaternary forms of porphobilinogen synthase
    Sabine Breinig
    Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, Pennsylvania 19111 2497, USA
    Nat Struct Biol 10:757-63. 2003
    ....
  11. ncbi request reprint 13C NMR studies of the enzyme-product complex of Bacillus subtilis chorismate mutase
    J S Rajagopalan
    Institute for Cancer Research, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111
    Biochemistry 32:3965-72. 1993
    ..abstract truncated at 250 words)..
  12. ncbi request reprint Porphobilinogen synthase from Escherichia coli is a Zn(II) metalloenzyme stimulated by Mg(II)
    L W Mitchell
    Institute for Cancer Research, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111
    Arch Biochem Biophys 300:169-77. 1993
    ..Li, and M. P. Timko (1991) J. Biol. Chem. 266, 17060-17066]. This work lays the foundation for identification of functional amino acids based on the sequence similarities between PBGS from bacterial, plant, and mammalian sources...
  13. pmc Allosteric inhibition of human porphobilinogen synthase
    Sarah H Lawrence
    Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA
    J Biol Chem 284:35807-17. 2009
    ..Data support the hypothesis that human PBGS hexamer stabilization may explain these side effects. The current work identifies allosteric ligands of human PBGS and, thus, identifies human PBGS as a medically relevant allosteric enzyme...
  14. pmc ALAD porphyria is a conformational disease
    Eileen K Jaffe
    Fox Chase Cancer Center, Philadelphia, PA 19111, USA
    Am J Hum Genet 80:329-37. 2007
    ..We propose that the disequilibrium of morpheein assemblies broadens the definition of conformational diseases beyond the prion disorders and that ALAD porphyria is the first example of a morpheein-based conformational disease...
  15. ncbi request reprint Morpheeins--a new structural paradigm for allosteric regulation
    Eileen K Jaffe
    BioMolecular Structure and Function Group, Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111, USA
    Trends Biochem Sci 30:490-7. 2005
    ..It is proposed here that the behavior of some other allosteric enzymes reflect dynamic morpheein equilibrium systems and six candidate proteins are enumerated...
  16. ncbi request reprint Abrogation of fibroblast activation protein enzymatic activity attenuates tumor growth
    Jonathan D Cheng
    Department of Medical Oncology, Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111 2497, USA
    Mol Cancer Ther 4:351-60. 2005
    ....
  17. pmc Plastid-associated porphobilinogen synthase from Toxoplasma gondii: kinetic and structural properties validate therapeutic potential
    Dhanasekaran Shanmugam
    Department of Biology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    J Biol Chem 285:22122-31. 2010
    ..The distinct phylogenetic, enzymatic, and structural features of apicomplexan PBGS offer scope for developing selective inhibitors of the parasite enzyme based on its quaternary structure characteristics...
  18. ncbi request reprint Single amino acid mutations alter the distribution of human porphobilinogen synthase quaternary structure isoforms (morpheeins)
    Lei Tang
    Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA
    J Biol Chem 281:6682-90. 2006
    ..The metastable nature of the R240A hexamer supports the hypothesis that octameric and hexameric morpheeins of PBGS are very close in energy. W19A assembles into a mixture of dimers, which appear to be stable...
  19. doi request reprint Kinetics and thermodynamics of the interchange of the morpheein forms of human porphobilinogen synthase
    Trevor Selwood
    Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, Pennsylvania 19111, USA
    Biochemistry 47:3245-57. 2008
    ....
  20. ncbi request reprint Substrate-induced interconversion of protein quaternary structure isoforms
    Lei Tang
    Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA
    J Biol Chem 280:15786-93. 2005
    ..This observation illustrates that the assembly and disassembly of oligomeric proteins can be facilitated by the protein motions that accompany enzymatic catalysis...
  21. ncbi request reprint A structural basis for half-of-the-sites metal binding revealed in Drosophila melanogaster porphobilinogen synthase
    Lenka Kundrat
    Institute for Cancer Research, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111 2497, USA
    J Biol Chem 278:31325-30. 2003
    ..5/subunit. This result reveals a structural basis for half-of-the-sites metal binding that is consistent with a reciprocating motion model for function of oligomeric PBGS...
  22. pmc Shape shifting leads to small-molecule allosteric drug discovery
    Sarah H Lawrence
    Fox Chase Cancer Center, Philadelphia, PA 19111, USA
    Chem Biol 15:586-96. 2008
    ..We propose that this strategy for inhibitor discovery can be applied to other proteins that use the morpheein model for allosteric regulation...
  23. ncbi request reprint delta-Aminolevulinate dehydratase (ALAD) porphyria: the first case in North America with two novel ALAD mutations
    Reiko Akagi
    Department of Nutritional Science, Okayama Prefectural University, Soja, Japan
    Mol Genet Metab 87:329-36. 2006
    ..This case represents the molecular analysis of the ALAD gene defects in the first case of ADP identified in North America, who is a compound heterozygote for two novel ALAD gene defects...
  24. pmc Rhodobacter capsulatus porphobilinogen synthase, a high activity metal ion independent hexamer
    David W Bollivar
    Department of Biology, Illinois Wesleyan University, P, O, Box 2900, Bloomington, IL 61702 2900, USA
    BMC Biochem 5:17. 2004
    ..This paper reports new information on the metal ion independence and quaternary structure of PBGS from the photosynthetic bacterium Rhodobacter capsulatus...