Evan T Powers

Summary

Affiliation: The Scripps Research Institute
Country: USA

Publications

  1. pmc The kinetics of nucleated polymerizations at high concentrations: amyloid fibril formation near and above the "supercritical concentration"
    Evan T Powers
    Department of Chemistry, The Scripps Research Institute, La Jolla, California 92037, USA
    Biophys J 91:122-32. 2006
  2. pmc The oxidative stress metabolite 4-hydroxynonenal promotes Alzheimer protofibril formation
    Sarah J Siegel
    The Scripps Research Institute, and The Skaggs Institute for Chemical Biology, 10550 North Torrey Pines Road, La Jolla, California 92037, USA
    Biochemistry 46:1503-10. 2007
  3. pmc Diversity in the origins of proteostasis networks--a driver for protein function in evolution
    Evan T Powers
    Department of Chemistry, The Scripps Research Institute, La Jolla, California 92037, USA
    Nat Rev Mol Cell Biol 14:237-48. 2013
  4. ncbi request reprint Diversity in the origins of proteostasis networks--a driver for protein function in evolution
    Evan T Powers
    Department of Chemistry, The Scripps Research Institute, La Jolla, California 92037, USA
    Nat Rev Mol Cell Biol 14:237-48. 2013
  5. pmc FoldEco: a model for proteostasis in E. coli
    Evan T Powers
    Department of Chemistry, The Scripps Research Institute, La Jolla, CA 92037, USA
    Cell Rep 1:265-76. 2012
  6. pmc Mechanisms of protein fibril formation: nucleated polymerization with competing off-pathway aggregation
    Evan T Powers
    Department of Chemistry, The Scripps Research Institute, La Jolla, California, USA
    Biophys J 94:379-91. 2008
  7. pmc A perspective on mechanisms of protein tetramer formation
    Evan T Powers
    Department of Chemistry, The Scripps Research Institute, La Jolla, California 92037, USA
    Biophys J 85:3587-99. 2003
  8. ncbi request reprint Costly mistakes: translational infidelity and protein homeostasis
    Evan T Powers
    Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Rd, La Jolla, CA 92037, USA
    Cell 134:204-6. 2008
  9. doi request reprint Biological and chemical approaches to diseases of proteostasis deficiency
    Evan T Powers
    Departments of Chemistry and Molecular and Experimental Medicine and the Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA
    Annu Rev Biochem 78:959-91. 2009
  10. pmc Protein native-state stabilization by placing aromatic side chains in N-glycosylated reverse turns
    Elizabeth K Culyba
    Department of Chemistry, The Scripps Research Institute, La Jolla, CA 92037, USA
    Science 331:571-5. 2011

Collaborators

Detail Information

Publications49

  1. pmc The kinetics of nucleated polymerizations at high concentrations: amyloid fibril formation near and above the "supercritical concentration"
    Evan T Powers
    Department of Chemistry, The Scripps Research Institute, La Jolla, California 92037, USA
    Biophys J 91:122-32. 2006
    ..We also derive a relation that can be used in a straightforward method for determining the nucleus size and the supercritical concentration from experimental measurements of fibril formation rates...
  2. pmc The oxidative stress metabolite 4-hydroxynonenal promotes Alzheimer protofibril formation
    Sarah J Siegel
    The Scripps Research Institute, and The Skaggs Institute for Chemical Biology, 10550 North Torrey Pines Road, La Jolla, California 92037, USA
    Biochemistry 46:1503-10. 2007
    ..These results provide further incentive to understand the role of oxidative stress and small-molecule Abeta modifications in sporadic AD...
  3. pmc Diversity in the origins of proteostasis networks--a driver for protein function in evolution
    Evan T Powers
    Department of Chemistry, The Scripps Research Institute, La Jolla, California 92037, USA
    Nat Rev Mol Cell Biol 14:237-48. 2013
    ....
  4. ncbi request reprint Diversity in the origins of proteostasis networks--a driver for protein function in evolution
    Evan T Powers
    Department of Chemistry, The Scripps Research Institute, La Jolla, California 92037, USA
    Nat Rev Mol Cell Biol 14:237-48. 2013
    ....
  5. pmc FoldEco: a model for proteostasis in E. coli
    Evan T Powers
    Department of Chemistry, The Scripps Research Institute, La Jolla, CA 92037, USA
    Cell Rep 1:265-76. 2012
    ..A web version of FoldEco is available at http://foldeco.scripps.edu...
  6. pmc Mechanisms of protein fibril formation: nucleated polymerization with competing off-pathway aggregation
    Evan T Powers
    Department of Chemistry, The Scripps Research Institute, La Jolla, California, USA
    Biophys J 94:379-91. 2008
    ....
  7. pmc A perspective on mechanisms of protein tetramer formation
    Evan T Powers
    Department of Chemistry, The Scripps Research Institute, La Jolla, California 92037, USA
    Biophys J 85:3587-99. 2003
    ..We propose that this could lead to undesirable consequences for an organism, and that selective pressure may have caused homotetrameric proteins to evolve to assemble by a single pathway...
  8. ncbi request reprint Costly mistakes: translational infidelity and protein homeostasis
    Evan T Powers
    Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Rd, La Jolla, CA 92037, USA
    Cell 134:204-6. 2008
    ....
  9. doi request reprint Biological and chemical approaches to diseases of proteostasis deficiency
    Evan T Powers
    Departments of Chemistry and Molecular and Experimental Medicine and the Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA
    Annu Rev Biochem 78:959-91. 2009
    ..We propose that such therapeutic strategies, including combination therapies, represent a new approach for treating a range of diverse human maladies...
  10. pmc Protein native-state stabilization by placing aromatic side chains in N-glycosylated reverse turns
    Elizabeth K Culyba
    Department of Chemistry, The Scripps Research Institute, La Jolla, CA 92037, USA
    Science 331:571-5. 2011
    ..Glycosylating this portable structural module, an enhanced aromatic sequon, in three different proteins stabilizes their native states by -0.7 to -2.0 kilocalories per mole and increases cellular glycosylation efficiency...
  11. ncbi request reprint Small molecule oxidation products trigger disease-associated protein misfolding
    Jan Bieschke
    The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA
    Acc Chem Res 39:611-9. 2006
    ..This Account explores the mechanism of small molecule oxidation product-mediated protein misassembly and possible intervention strategies...
  12. pmc Site-specific modification of Alzheimer's peptides by cholesterol oxidation products enhances aggregation energetics and neurotoxicity
    Kenji Usui
    Departments of Chemistry and Molecular and Experimental Medicine, Scripps Research Institute and Skaggs Institute for Chemical Biology, La Jolla, CA 92037, USA
    Proc Natl Acad Sci U S A 106:18563-8. 2009
    ....
  13. ncbi request reprint Understanding the mechanism of beta-sheet folding from a chemical and biological perspective
    Marcus Jager
    Department of Chemistry, Skaggs Institute of Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA
    Biopolymers 90:751-8. 2008
    ..These insights have allowed the design of Pin1 WW domains that fold at rates that approach the theoretical speed limit of folding...
  14. ncbi request reprint Oxidative metabolites accelerate Alzheimer's amyloidogenesis by a two-step mechanism, eliminating the requirement for nucleation
    Jan Bieschke
    The Scripps Research Institute, La Jolla, California 92037, USA
    Biochemistry 44:4977-83. 2005
    ..Metabolite-initiated amyloidogenesis offers an explanation for how Abeta aggregation could occur at physiological nanomolar concentrations...
  15. ncbi request reprint Transthyretin aggregation under partially denaturing conditions is a downhill polymerization
    Amy R Hurshman
    Department of Chemistry and Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road BCC 506, La Jolla, California 92037, USA
    Biochemistry 43:7365-81. 2004
    ....
  16. pmc Structural and energetic basis of carbohydrate-aromatic packing interactions in proteins
    Wentao Chen
    Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California 92037, USA
    J Am Chem Soc 135:9877-84. 2013
    ..Thus, tight binding of carbohydrates and aromatic residues is driven by the hydrophobic effect and CH-π interactions featuring a dominating dispersive component. ..
  17. ncbi request reprint An adaptable standard for protein export from the endoplasmic reticulum
    R Luke Wiseman
    Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
    Cell 131:809-21. 2007
    ..Instead, a network view provides insight into the basis for cellular diversity, disease origins, and protein homeostasis, and predicts strategies for restoring protein homeostasis in protein-misfolding diseases...
  18. ncbi request reprint Potent and selective structure-based dibenzofuran inhibitors of transthyretin amyloidogenesis: kinetic stabilization of the native state
    H Michael Petrassi
    Department of Chemistry and The Skaggs Institute of Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, BCC265, La Jolla, CA 92037, USA
    J Am Chem Soc 127:6662-71. 2005
    ..It is now established that the dibenzofuran-based amyloidogenesis inhibitors have high selectivity, affinity, and efficacy and are thus excellent candidates for further pharmacologic evaluation...
  19. ncbi request reprint Prevention of transthyretin amyloid disease by changing protein misfolding energetics
    Per Hammarstrom
    Department of Chemistry and The Skaggs Institute of Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
    Science 299:713-6. 2003
    ....
  20. pmc Heparin binds 8 kDa gelsolin cross-β-sheet oligomers and accelerates amyloidogenesis by hastening fibril extension
    James P Solomon
    Department of Chemistry and Molecular and Experimental Medicine and Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, United States
    Biochemistry 50:2486-98. 2011
    ....
  21. pmc Localized thermodynamic coupling between hydrogen bonding and microenvironment polarity substantially stabilizes proteins
    Jianmin Gao
    Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, California, USA
    Nat Struct Mol Biol 16:684-90. 2009
    ....
  22. pmc Partitioning conformational intermediates between competing refolding and aggregation pathways: insights into transthyretin amyloid disease
    R Luke Wiseman
    Department of Chemistry and The Skaggs Institute of Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, BCC 265, La Jolla, California 92037, USA
    Biochemistry 44:16612-23. 2005
    ..This shift from efficient to inefficient aggregate clearance could occur with aging, offering an explanation for the age-associated nature of these neurodegenerative diseases...
  23. pmc Influence of the N-terminal domain on the aggregation properties of the prion protein
    Kristen N Frankenfield
    Department of Chemistry and Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA
    Protein Sci 14:2154-66. 2005
    ....
  24. ncbi request reprint Controlling the morphology of cross beta-sheet assemblies by rational design
    Songpon Deechongkit
    Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA
    J Am Chem Soc 127:8562-70. 2005
    ..These widths can be controlled by changing the length of the peptide strands. Further assembly of the filaments into fibrils or ribbons can be controlled by modification of the template, C-terminus, and buffer ion composition...
  25. ncbi request reprint Design, synthesis, and evaluation of oxazole transthyretin amyloidogenesis inhibitors
    Hossein Razavi
    Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, BCC265, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
    Bioorg Med Chem Lett 15:1075-8. 2005
    ..The CF(3) substitution at C(5) also improves the TTR binding selectivity over all the other proteins in human blood...
  26. pmc Quantification of transthyretin kinetic stability in human plasma using subunit exchange
    Irit Rappley
    Department of Chemistry, The Skaggs Institute for Chemical Biology, Department of Molecular and Experimental Medicine, and Department of Chemical Physiology, The Scripps Research Institute, La Jolla, California 92037, United States
    Biochemistry 53:1993-2006. 2014
    ..TTR kinetic stability correlated with the tafamidis plasma concentration. ..
  27. ncbi request reprint Context-dependent contributions of backbone hydrogen bonding to beta-sheet folding energetics
    Songpon Deechongkit
    Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, BCC 506, La Jolla, California 92037, USA
    Nature 430:101-5. 2004
    ..Collectively, our results provide an unusually detailed picture of the folding of a beta-sheet protein...
  28. pmc The 8 and 5 kDa fragments of plasma gelsolin form amyloid fibrils by a nucleated polymerization mechanism, while the 68 kDa fragment is not amyloidogenic
    James P Solomon
    Department of Chemistry, Skaggs Institute for Chemical Biology, La Jolla, California 92037, USA
    Biochemistry 48:11370-80. 2009
    ....
  29. pmc Glycosylation of the enhanced aromatic sequon is similarly stabilizing in three distinct reverse turn contexts
    JOSHUA L PRICE
    Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
    Proc Natl Acad Sci U S A 108:14127-32. 2011
    ..Adding the Phe-Asn-Xxx-Thr motif (in a type I' β-turn) to the enhanced aromatic sequon family doubles the number of proteins that can be stabilized by glycosylation without having to alter the native reverse turn type...
  30. pmc Aromatic sulfonyl fluorides covalently kinetically stabilize transthyretin to prevent amyloidogenesis while affording a fluorescent conjugate
    Neil P Grimster
    Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA
    J Am Chem Soc 135:5656-68. 2013
    ..Eleven of the TTR covalent kinetic stabilizers synthesized exhibit fluorescence upon conjugation and therefore could have imaging applications as a consequence of the environment sensitive fluorescence of the chromophore...
  31. pmc The transthyretin amyloidoses: from delineating the molecular mechanism of aggregation linked to pathology to a regulatory-agency-approved drug
    Steven M Johnson
    Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA
    J Mol Biol 421:185-203. 2012
    ..Here we review the biophysical basis for the kinetic stabilization strategy and the structure-based drug design effort that led to this first-in-class pharmacologic agent...
  32. pmc Amyloid-β forms fibrils by nucleated conformational conversion of oligomers
    Jiyong Lee
    Department of Chemistry, The Scripps Research Institute and The Skaggs Institute for Chemical Biology, La Jolla, California, USA
    Nat Chem Biol 7:602-9. 2011
    ....
  33. pmc Context-dependent effects of asparagine glycosylation on Pin WW folding kinetics and thermodynamics
    JOSHUA L PRICE
    Department of Chemistry, Scripps Research Institute, La Jolla, California 92037, United States
    J Am Chem Soc 132:15359-67. 2010
    ..Our data are consistent with the hypothesis that specific, evolved protein-glycan contacts must also play an important role in mediating the beneficial energetic effects on protein folding that glycosylation can confer...
  34. ncbi request reprint ALS mutants of human superoxide dismutase form fibrous aggregates via framework destabilization
    Michael DiDonato
    Department of Molecular Biology, The Skaggs Institute for Chemical Biology, The Scripps Research Institute, Maildrop MB4, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
    J Mol Biol 332:601-15. 2003
    ....
  35. ncbi request reprint Elevated levels of oxidized cholesterol metabolites in Lewy body disease brains accelerate alpha-synuclein fibrilization
    Daryl A Bosco
    Department of Chemistry and The Skaggs Institute of Chemical Biology, The Scripps Research Institute, 10550 N Torrey Pines Road, La Jolla, California 92037, USA
    Nat Chem Biol 2:249-53. 2006
    ..By extension, these data lead to the hypothesis that oxidative stress produces cholesterol aldehydes that enable alpha-synuclein aggregation, leading to a pathologic cycle...
  36. ncbi request reprint Fluorogenic small molecules requiring reaction with a specific protein to create a fluorescent conjugate for biological imaging-what we know and what we need to learn
    Aleksandra Baranczak
    Department of Chemistry, The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA, 92037 Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA, 92037
    Biopolymers 101:484-95. 2014
    ..2013 Wiley Periodicals, Inc. Biopolymers 101: 484-495, 2014. ..
  37. ncbi request reprint Benzoxazoles as transthyretin amyloid fibril inhibitors: synthesis, evaluation, and mechanism of action
    Hossein Razavi
    Department of Chemistry, The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA
    Angew Chem Int Ed Engl 42:2758-61. 2003
  38. pmc Evaluating beta-turn mimics as beta-sheet folding nucleators
    Amelia A Fuller
    Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
    Proc Natl Acad Sci U S A 106:11067-72. 2009
    ..These beta-turn mimics can now be used to interrogate protein folding transition state structures and the 2 kinetic analyses presented can be used to assess the nucleation capacity of other beta-turn mimics...
  39. pmc The core trisaccharide of an N-linked glycoprotein intrinsically accelerates folding and enhances stability
    Sarah R Hanson
    Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
    Proc Natl Acad Sci U S A 106:3131-6. 2009
    ..The native state stabilization and decreased activation barrier for folding conferred by N-glycosylation provide a powerful and potentially general mechanism for enhancing folding in the secretory pathway...
  40. pmc Metabolite-initiated protein misfolding may trigger Alzheimer's disease
    Qinghai Zhang
    Department of Chemistry and The Skaggs Institute of Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
    Proc Natl Acad Sci U S A 101:4752-7. 2004
    ....
  41. pmc The proteostasis boundary in misfolding diseases of membrane traffic
    Darren M Hutt
    Department of Cell Biology, The Scripps Research Institute, La Jolla, CA 92037, USA
    FEBS Lett 583:2639-46. 2009
    ..We discuss how manipulation of the folding energetics or the PB through metabolites and pharmacological intervention provides multiple routes for restoration of biological function in trafficking disease...
  42. pmc Sequence-dependent denaturation energetics: A major determinant in amyloid disease diversity
    Per Hammarstrom
    Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road BCC265, La Jolla, CA 92037, USA
    Proc Natl Acad Sci U S A 99:16427-32. 2002
    ....
  43. ncbi request reprint Characterizing the altered cellular proteome induced by the stress-independent activation of heat shock factor 1
    Lisa M Ryno
    Department of Molecular and Experimental Medicine, Department of Chemical Physiology, The Scripps Research Institute, La Jolla, California 92037, United States
    ACS Chem Biol 9:1273-83. 2014
    ....
  44. ncbi request reprint Synthesis, structure, and activity of diclofenac analogues as transthyretin amyloid fibril formation inhibitors
    Vibha B Oza
    Department of Chemistry and The Skaggs Institute of Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, BCC 265, La Jolla, California 92037, USA
    J Med Chem 45:321-32. 2002
    ..High-resolution X-ray crystal structures of four of the active compounds bound to TTR were obtained. These demonstrate the significant flexibility with which TTR can accommodate ligands within its two binding sites...
  45. pmc N-PEGylation of a Reverse Turn Is Stabilizing in Multiple Sequence Contexts, unlike N-GlcNAcylation
    JOSHUA L PRICE
    Department of Chemistry, The Skaggs Institute for Chemical Biology, and Department of Molecular and Experimental Medicine, The Scripps Research Institute, 10550 N Torrey Pines Rd, La Jolla, California 92037, United States
    ACS Chem Biol 6:1188-92. 2011
    ....
  46. pmc Aβ induces astrocytic glutamate release, extrasynaptic NMDA receptor activation, and synaptic loss
    Maria Talantova
    Del E Webb Center for Neuroscience, Aging, and Stem Cell Research, Sanford Burnham Medical Research Institute, La Jolla, CA 92037, USA
    Proc Natl Acad Sci U S A 110:E2518-27. 2013
    ..Importantly, the improved NMDAR antagonist NitroMemantine, which selectively inhibits extrasynaptic over physiological synaptic NMDAR activity, protects synapses from Aβ-induced damage both in vitro and in vivo. ..
  47. ncbi request reprint Ordered Langmuir-Blodgett films of amphiphilic beta-hairpin peptides imaged by atomic force microscopy
    Evan T Powers
    Department of Chemistry and The Skaggs Institute of Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA
    Angew Chem Int Ed Engl 41:127-30. 2002
  48. ncbi request reprint Adsorption of beta-hairpin peptides on the surface of water: a neutron reflection study
    Jian R Lu
    Biological Physics Group, Department of Physics, UMIST, PO Box 88, Manchester M60 1QD, UK
    J Am Chem Soc 125:3751-7. 2003
    ..The results strongly suggest that the 14-mer peptide monolayers were fully afloat on the surface of water, with only the carboxy groups on Glu residues hydrated...
  49. pmc Quantification of the thermodynamically linked quaternary and tertiary structural stabilities of transthyretin and its disease-associated variants: the relationship between stability and amyloidosis
    Amy R Hurshman Babbes
    Joint Science Department, Claremont McKenna, Pitzer, and Scripps Colleges, 925 North Mills Avenue, Claremont, California 91711, USA
    Biochemistry 47:6969-84. 2008
    ..The observed differences in stability among the disease-associated TTR variants highlight the complexity and heterogeneity of TTR amyloid disease, an observation that has important implications for the treatment of these maladies...