Shining light on cysteine modification: connecting protein conformational dynamics to catalysis and regulation
Abstract
We report that cysteine is a rare but functionally important amino acid that is often subject to covalent modification. Cysteine oxidation plays an important role in many human disease processes, and basal levels of cysteine oxidation are required for proper cellular function. Because reactive cysteine residues are typically ionized to the thiolate anion (Cys-S-), their formation of a covalent bond alters the electrostatic and steric environment of the active site. X-ray-induced photo-oxidation to sulfenic acids (Cys-SOH) can recapitulate some aspects of the changes that occur under physiological conditions. Here we propose how site-specific cysteine photo-oxidation can be used to interrogate ensuing changes in protein structure and dynamics at atomic resolution. Although this powerful approach can connect cysteine covalent modification to global protein conformational changes and function, careful biochemical validation must accompany all such studies to exclude misleading artifacts. Lastly, new types of X-ray crystallography experiments and powerful computational methods are creating new opportunities to connect conformational dynamics to catalysis for the large class of systems that use covalently modified cysteine residues for catalysis or regulation.
- Authors:
-
[1];
- SLAC National Accelerator Lab., Menlo Park, CA (United States); Stanford Univ., CA (United States); Univ. of California, San Francisco, CA (United States)
- Univ. of Nebraska, Lincoln, NE (United States)
- Publication Date:
- Research Org.:
- SLAC National Accelerator Lab., Menlo Park, CA (United States)
- Sponsoring Org.:
- USDOE
- OSTI Identifier:
- 1546912
- Grant/Contract Number:
- AC02-76SF00515
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Journal of Synchrotron Radiation (Online)
- Additional Journal Information:
- Journal Name: Journal of Synchrotron Radiation (Online); Journal Volume: 26; Journal Issue: 4; Journal ID: ISSN 1600-5775
- Publisher:
- International Union of Crystallography
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY; 59 BASIC BIOLOGICAL SCIENCES; cysteine modification; radiation-controlled photo-oxidation; serial X-ray crystallography; enzyme conformational dynamics; molecular dynamics simulations
Citation Formats
van den Bedem, Henry, and Wilson, Mark A. Shining light on cysteine modification: connecting protein conformational dynamics to catalysis and regulation. United States: N. p., 2019.
Web. doi:10.1107/s160057751900568x.
van den Bedem, Henry, & Wilson, Mark A. Shining light on cysteine modification: connecting protein conformational dynamics to catalysis and regulation. United States. doi:10.1107/s160057751900568x.
van den Bedem, Henry, and Wilson, Mark A. Thu .
"Shining light on cysteine modification: connecting protein conformational dynamics to catalysis and regulation". United States. doi:10.1107/s160057751900568x. https://www.osti.gov/servlets/purl/1546912.
@article{osti_1546912,
title = {Shining light on cysteine modification: connecting protein conformational dynamics to catalysis and regulation},
author = {van den Bedem, Henry and Wilson, Mark A.},
abstractNote = {We report that cysteine is a rare but functionally important amino acid that is often subject to covalent modification. Cysteine oxidation plays an important role in many human disease processes, and basal levels of cysteine oxidation are required for proper cellular function. Because reactive cysteine residues are typically ionized to the thiolate anion (Cys-S-), their formation of a covalent bond alters the electrostatic and steric environment of the active site. X-ray-induced photo-oxidation to sulfenic acids (Cys-SOH) can recapitulate some aspects of the changes that occur under physiological conditions. Here we propose how site-specific cysteine photo-oxidation can be used to interrogate ensuing changes in protein structure and dynamics at atomic resolution. Although this powerful approach can connect cysteine covalent modification to global protein conformational changes and function, careful biochemical validation must accompany all such studies to exclude misleading artifacts. Lastly, new types of X-ray crystallography experiments and powerful computational methods are creating new opportunities to connect conformational dynamics to catalysis for the large class of systems that use covalently modified cysteine residues for catalysis or regulation.},
doi = {10.1107/s160057751900568x},
journal = {Journal of Synchrotron Radiation (Online)},
number = 4,
volume = 26,
place = {United States},
year = {2019},
month = {6}
}
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Works referenced in this record:
Formation of a Stabilized Cysteine Sulfinic Acid Is Critical for the Mitochondrial Function of the Parkinsonism Protein DJ-1
journal, January 2009
- Blackinton, Jeff; Lakshminarasimhan, Mahadevan; Thomas, Kelly J.
- Journal of Biological Chemistry, Vol. 284, Issue 10
X-ray-induced photo-chemistry and X-ray absorption spectroscopy of biological samples
journal, October 2012
- George, Graham N.; Pickering, Ingrid J.; Pushie, M. Jake
- Journal of Synchrotron Radiation, Vol. 19, Issue 6
Structural enzymology using X-ray free electron lasers
journal, December 2016
- Kupitz, Christopher; Olmos, Jose L.; Holl, Mark
- Structural Dynamics, Vol. 4, Issue 4
Immunostaining of Oxidized DJ-1 in Human and Mouse Brains
journal, July 2014
- Saito, Yoshiro; Miyasaka, Tomohiro; Hatsuta, Hiroyuki
- Journal of Neuropathology & Experimental Neurology, Vol. 73, Issue 7
Conformational variation of proteins at room temperature is not dominated by radiation damage
journal, January 2017
- Russi, Silvia; González, Ana; Kenner, Lillian R.
- Journal of Synchrotron Radiation, Vol. 24, Issue 1
Very fast empirical prediction and rationalization of protein pKa values
journal, October 2005
- Li, Hui; Robertson, Andrew D.; Jensen, Jan H.
- Proteins: Structure, Function, and Bioinformatics, Vol. 61, Issue 4
Reversible Cysteine Oxidation in Hydrogen Peroxide Sensing and Signal Transduction
journal, April 2014
- García-Santamarina, Sarela; Boronat, Susanna; Hidalgo, Elena
- Biochemistry, Vol. 53, Issue 16
Identification of Cyanamide-Based Janus Kinase 3 (JAK3) Covalent Inhibitors
journal, November 2018
- Casimiro-Garcia, Agustin; Trujillo, John I.; Vajdos, Felix
- Journal of Medicinal Chemistry, Vol. 61, Issue 23
Preferred Hydrogen-Bonding Partners of Cysteine: Implications for Regulating Cys Functions
journal, September 2016
- Mazmanian, Karine; Sargsyan, Karen; Grauffel, Cédric
- The Journal of Physical Chemistry B, Vol. 120, Issue 39
K-Ras(G12C) inhibitors allosterically control GTP affinity and effector interactions
journal, November 2013
- Ostrem, Jonathan M.; Peters, Ulf; Sos, Martin L.
- Nature, Vol. 503, Issue 7477
Integrative, dynamic structural biology at atomic resolution—it's about time
journal, March 2015
- van den Bedem, Henry; Fraser, James S.
- Nature Methods, Vol. 12, Issue 4
Understanding the p K a of Redox Cysteines: The Key Role of Hydrogen Bonding
journal, January 2013
- Roos, Goedele; Foloppe, Nicolas; Messens, Joris
- Antioxidants & Redox Signaling, Vol. 18, Issue 1
The role of dimer asymmetry and protomer dynamics in enzyme catalysis
journal, January 2017
- Kim, Tae Hun; Mehrabi, Pedram; Ren, Zhong
- Science, Vol. 355, Issue 6322
Emerging and Re-Emerging Warheads for Targeted Covalent Inhibitors: Applications in Medicinal Chemistry and Chemical Biology
journal, December 2018
- Gehringer, Matthias; Laufer, Stefan A.
- Journal of Medicinal Chemistry, Vol. 62, Issue 12
Electric-field-stimulated protein mechanics
journal, December 2016
- Hekstra, Doeke R.; White, K. Ian; Socolich, Michael A.
- Nature, Vol. 540, Issue 7633
Roles of Aspartic Acid-181 and Serine-222 in Intermediate Formation and Hydrolysis of the Mammalian Protein-Tyrosine-Phosphatase PTP1 †
journal, April 1997
- Lohse, Daniel L.; Denu, John M.; Santoro, Nicholas
- Biochemistry, Vol. 36, Issue 15
Outrunning free radicals in room-temperature macromolecular crystallography
journal, June 2012
- Owen, Robin L.; Axford, Danny; Nettleship, Joanne E.
- Acta Crystallographica Section D Biological Crystallography, Vol. 68, Issue 7
Isocyanides and cyanides as natural products
journal, October 1992
- Scheuer, Paul J.
- Accounts of Chemical Research, Vol. 25, Issue 10
Predicting the X-ray lifetime of protein crystals
journal, December 2013
- Zeldin, O. B.; Brockhauser, S.; Bremridge, J.
- Proceedings of the National Academy of Sciences, Vol. 110, Issue 51
Protein tyrosine phosphatase structure-function relationships in regulation and pathogenesis: Protein tyrosine phosphatase structure-function
journal, July 2012
- Böhmer, Frank; Szedlacsek, Stefan; Tabernero, Lydia
- FEBS Journal, Vol. 280, Issue 2
Protein Promiscuity in H 2 O 2 Signaling
journal, April 2019
- Young, David; Pedre, Brandan; Ezeriņa, Daria
- Antioxidants & Redox Signaling, Vol. 30, Issue 10
Expanding the functional diversity of proteins through cysteine oxidation
journal, December 2008
- Reddie, Khalilah G.; Carroll, Kate S.
- Current Opinion in Chemical Biology, Vol. 12, Issue 6
Covalent inhibitors in drug discovery: from accidental discoveries to avoided liabilities and designed therapies
journal, September 2015
- Bauer, Renato A.
- Drug Discovery Today, Vol. 20, Issue 9
DJ-1 as a human oncogene and potential therapeutic target
journal, February 2015
- Cao, Ji; Lou, Siyue; Ying, Meidan
- Biochemical Pharmacology, Vol. 93, Issue 3
Critical Assessment of the Strength of Hydrogen Bonds between the Sulfur Atom of Methionine/Cysteine and Backbone Amides in Proteins
journal, April 2015
- Mundlapati, V. Rao; Ghosh, Sanat; Bhattacherjee, Aditi
- The Journal of Physical Chemistry Letters, Vol. 6, Issue 8
Thermodynamic and Structural Characterization of the Specific Binding of Zn(II) to Human Protein DJ-1
journal, April 2014
- Tashiro, Shinya; Caaveiro, Jose M. M.; Wu, Chun-Xiang
- Biochemistry, Vol. 53, Issue 14
Cysteine p K a Depression by a Protonated Glutamic Acid in Human DJ-1 † ‡
journal, July 2008
- Witt, Anna C.; Lakshminarasimhan, Mahadevan; Remington, Benjamin C.
- Biochemistry, Vol. 47, Issue 28
Mutations in the DJ-1 Gene Associated with Autosomal Recessive Early-Onset Parkinsonism
journal, November 2002
- Bonifati, V.
- Science, Vol. 299, Issue 5604
Time-resolved serial crystallography captures high-resolution intermediates of photoactive yellow protein
journal, December 2014
- Tenboer, Jason; Basu, Shibom; Zatsepin, Nadia
- Science, Vol. 346, Issue 6214
The Catalytic Pathway of Cytochrome P450cam at Atomic Resolution
journal, March 2000
- Schlichting, I.
- Science, Vol. 287, Issue 5458
X-ray radiation-induced addition of oxygen atoms to protein residues: Visualization of Oxidation and Peroxidation of Protein Residues
journal, July 2016
- Wang, Jimin
- Protein Science, Vol. 25, Issue 8
PTP1B: a double agent in metabolism and oncogenesis
journal, August 2010
- Yip, Shu-Chin; Saha, Sayanti; Chernoff, Jonathan
- Trends in Biochemical Sciences, Vol. 35, Issue 8
Biomolecular Simulation: A Computational Microscope for Molecular Biology
journal, June 2012
- Dror, Ron O.; Dirks, Robert M.; Grossman, J. P.
- Annual Review of Biophysics, Vol. 41, Issue 1
Parkinsonism-associated Protein DJ-1/Park7 Is a Major Protein Deglycase That Repairs Methylglyoxal- and Glyoxal-glycated Cysteine, Arginine, and Lysine Residues
journal, November 2014
- Richarme, Gilbert; Mihoub, Mouadh; Dairou, Julien
- Journal of Biological Chemistry, Vol. 290, Issue 3
Rates of thiol-disulfide interchange reactions between mono- and dithiols and Ellman's reagent
journal, January 1977
- Whitesides, George M.; Lilburn, Jennifer E.; Szajewski, Richard P.
- The Journal of Organic Chemistry, Vol. 42, Issue 2
Exposing Hidden Alternative Backbone Conformations in X-ray Crystallography Using qFit
journal, October 2015
- Keedy, Daniel A.; Fraser, James S.; van den Bedem, Henry
- PLOS Computational Biology, Vol. 11, Issue 10
How Reactive are Druggable Cysteines in Protein Kinases?
journal, August 2018
- Awoonor-Williams, Ernest; Rowley, Christopher N.
- Journal of Chemical Information and Modeling, Vol. 58, Issue 9
Conformational dynamics of a crystalline protein from microsecond-scale molecular dynamics simulations and diffuse X-ray scattering
journal, December 2014
- Wall, Michael E.; Van Benschoten, Andrew H.; Sauter, Nicholas K.
- Proceedings of the National Academy of Sciences, Vol. 111, Issue 50
Intrinsic motions along an enzymatic reaction trajectory
journal, November 2007
- Henzler-Wildman, Katherine A.; Thai, Vu; Lei, Ming
- Nature, Vol. 450, Issue 7171
Oxidation state of the active-site cysteine in protein tyrosine phosphatase 1B
journal, June 2003
- van Montfort, Rob L. M.; Congreve, Miles; Tisi, Dominic
- Nature, Vol. 423, Issue 6941
Redox regulation of protein tyrosine phosphatase 1B involves a sulphenyl-amide intermediate
journal, June 2003
- Salmeen, Annette; Andersen, Jannik N.; Myers, Michael P.
- Nature, Vol. 423, Issue 6941
Inside the human cancer tyrosine phosphatome
journal, December 2010
- Julien, Sofi G.; Dubé, Nadia; Hardy, Serge
- Nature Reviews Cancer, Vol. 11, Issue 1
Absence of DJ-1 causes age-related retinal abnormalities in association with increased oxidative stress
journal, March 2017
- Bonilha, Vera L.; Bell, Brent A.; Rayborn, Mary E.
- Free Radical Biology and Medicine, Vol. 104
ROS-dependent regulation of Parkin and DJ-1 localization during oxidative stress in neurons
journal, August 2012
- Joselin, Alvin P.; Hewitt, Sarah J.; Callaghan, Steve M.
- Human Molecular Genetics, Vol. 21, Issue 22
Protein Topology Determines Cysteine Oxidation Fate: The Case of Sulfenyl Amide Formation among Protein Families
journal, March 2015
- Defelipe, Lucas A.; Lanzarotti, Esteban; Gauto, Diego
- PLOS Computational Biology, Vol. 11, Issue 3
Mapping the conformational landscape of a dynamic enzyme by multitemperature and XFEL crystallography
journal, September 2015
- Keedy, Daniel A.; Kenner, Lillian R.; Warkentin, Matthew
- eLife, Vol. 4
Intracellular metal binding and redox behavior of human DJ-1
journal, December 2017
- Barbieri, Letizia; Luchinat, Enrico; Banci, Lucia
- JBIC Journal of Biological Inorganic Chemistry, Vol. 23, Issue 1
Evolution of New Enzymatic Function by Structural Modulation of Cysteine Reactivity in Pseudomonas fluorescens Isocyanide Hydratase
journal, July 2010
- Lakshminarasimhan, Mahadevan; Madzelan, Peter; Nan, Ruth
- Journal of Biological Chemistry, Vol. 285, Issue 38
Pro-Survival Role for Parkinson's Associated Gene DJ-1 Revealed in Trophically Impaired Dopaminergic Neurons
journal, April 2010
- Aron, Liviu; Klein, Pontus; Pham, Thu-Trang
- PLoS Biology, Vol. 8, Issue 4
DJ-1, a Novel Oncogene Which Transforms Mouse NIH3T3 Cells in Cooperation withras
journal, February 1997
- Nagakubo, Daisuke; Taira, Takahiro; Kitaura, Hirotake
- Biochemical and Biophysical Research Communications, Vol. 231, Issue 2
Radiolytic Modification of Sulfur-Containing Amino Acid Residues in Model Peptides: Fundamental Studies for Protein Footprinting
journal, April 2005
- Xu, Guozhong; Chance, Mark R.
- Analytical Chemistry, Vol. 77, Issue 8
Chemical Probe To Monitor the Parkinsonism-Associated Protein DJ-1 in Live Cells
journal, July 2018
- Drechsel, Jonas; Mandl, Franziska A.; Sieber, Stephan A.
- ACS Chemical Biology, Vol. 13, Issue 8
Modeling discrete heterogeneity in X-ray diffraction data by fitting multi-conformers
journal, September 2009
- van den Bedem, Henry; Dhanik, Ankur; Latombe, Jean-Claude
- Acta Crystallographica Section D Biological Crystallography, Vol. 65, Issue 10
Oxidant stress evoked by pacemaking in dopaminergic neurons is attenuated by DJ-1
journal, November 2010
- Guzman, Jaime N.; Sanchez-Padilla, Javier; Wokosin, David
- Nature, Vol. 468, Issue 7324
Kinematic Flexibility Analysis: Hydrogen Bonding Patterns Impart a Spatial Hierarchy of Protein Motion
journal, September 2018
- Budday, Dominik; Leyendecker, Sigrid; van den Bedem, Henry
- Journal of Chemical Information and Modeling, Vol. 58, Issue 10
qFit-ligand Reveals Widespread Conformational Heterogeneity of Drug-Like Molecules in X-Ray Electron Density Maps
journal, November 2018
- van Zundert, Gydo C. P.; Hudson, Brandi M.; de Oliveira, Saulo H. P.
- Journal of Medicinal Chemistry, Vol. 61, Issue 24
Journey to the center of the protein: allostery from multitemperature multiconformer X-ray crystallography
journal, January 2019
- Keedy, Daniel A.
- Acta Crystallographica Section D Structural Biology, Vol. 75, Issue 2
RIDL : a tool to investigate radiation-induced density loss
journal, May 2018
- Bury, Charles Simon; Garman, Elspeth Frances
- Journal of Applied Crystallography, Vol. 51, Issue 3
Millisecond Radiolytic Modification of Peptides by Synchrotron X-rays Identified by Mass Spectrometry
journal, September 1999
- Maleknia, Simin D.; Brenowitz, Michael; Chance, Mark R.
- Analytical Chemistry, Vol. 71, Issue 18
Human DJ-1 and its homologs are novel glyoxalases
journal, April 2012
- Lee, Ju-young; Song, Jeeyeon; Kwon, Kyu
- Human Molecular Genetics, Vol. 21, Issue 14
Automated identification of functional dynamic contact networks from X-ray crystallography
journal, August 2013
- van den Bedem, Henry; Bhabha, Gira; Yang, Kun
- Nature Methods, Vol. 10, Issue 9
A proton relay enhances H2O2 sensitivity of GAPDH to facilitate metabolic adaptation
journal, January 2015
- Peralta, David; Bronowska, Agnieszka K.; Morgan, Bruce
- Nature Chemical Biology, Vol. 11, Issue 2
The Oxidation States of DJ-1 Dictate the Cell Fate in Response to Oxidative Stress Triggered by 4-HPR: Autophagy or Apoptosis?
journal, October 2014
- Cao, Ji; Ying, Meidan; Xie, Nan
- Antioxidants & Redox Signaling, Vol. 21, Issue 10
The 1.1-A resolution crystal structure of DJ-1, the protein mutated in autosomal recessive early onset Parkinson's disease
journal, July 2003
- Wilson, M. A.; Collins, J. L.; Hod, Y.
- Proceedings of the National Academy of Sciences, Vol. 100, Issue 16
Covalent targeting of acquired cysteines in cancer
journal, February 2016
- Visscher, Marieke; Arkin, Michelle R.; Dansen, Tobias B.
- Current Opinion in Chemical Biology, Vol. 30
Parkinson's disease-related DJ-1 modulates the expression of uncoupling protein 4 against oxidative stress
journal, April 2018
- Xu, Shaoqing; Yang, Xiaodong; Qian, Yiwei
- Journal of Neurochemistry, Vol. 145, Issue 4
The Parkinson's disease protein DJ-1 is neuroprotective due to cysteine-sulfinic acid-driven mitochondrial localization
journal, June 2004
- Canet-Avilés, Rosa M.; Wilson, Mark A.; Miller, David W.
- Proceedings of the National Academy of Sciences, Vol. 101, Issue 24
DJ-1 deficiency in astrocytes selectively enhances mitochondrial Complex I inhibitor-induced neurotoxicity: Astrocyte DJ-1 loss enhances neurotoxicity
journal, January 2011
- Mullett, Steven J.; Hinkle, David A.
- Journal of Neurochemistry, Vol. 117, Issue 3
Molecular dynamics simulation of triclinic lysozyme in a crystal lattice: Molecular Dynamics of Crystal Lysozyme
journal, June 2015
- Janowski, Pawel A.; Liu, Chunmei; Deckman, Jason
- Protein Science, Vol. 25, Issue 1
Developing Irreversible Inhibitors of the Protein Kinase Cysteinome
journal, February 2013
- Liu, Qingsong; Sabnis, Yogesh; Zhao, Zheng
- Chemistry & Biology, Vol. 20, Issue 2
Discovery and Optimization of Inhibitors of the Parkinson’s Disease Associated Protein DJ-1
journal, July 2018
- Tashiro, Shinya; Caaveiro, Jose M. M.; Nakakido, Makoto
- ACS Chemical Biology, Vol. 13, Issue 9
Geometric analysis characterizes molecular rigidity in generic and non-generic protein configurations
journal, October 2015
- Budday, Dominik; Leyendecker, Sigrid; van den Bedem, Henry
- Journal of the Mechanics and Physics of Solids, Vol. 83
Shoot-and-Trap: Use of specific x-ray damage to study structural protein dynamics by temperature-controlled cryo-crystallography
journal, August 2008
- Colletier, J. -P.; Bourgeois, D.; Sanson, B.
- Proceedings of the National Academy of Sciences, Vol. 105, Issue 33
Accessing protein conformational ensembles using room-temperature X-ray crystallography
journal, September 2011
- Fraser, J. S.; van den Bedem, H.; Samelson, A. J.
- Proceedings of the National Academy of Sciences, Vol. 108, Issue 39
Reconciling the chemistry and biology of reactive oxygen species
journal, April 2008
- Winterbourn, Christine C.
- Nature Chemical Biology, Vol. 4, Issue 5
Molecular Basis for Redox Activation of Epidermal Growth Factor Receptor Kinase
journal, July 2016
- Truong, Thu H.; Ung, Peter Man-Un; Palde, Prakash B.
- Cell Chemical Biology, Vol. 23, Issue 7
Hydrogen peroxide sensing, signaling and regulation of transcription factors
journal, January 2014
- Marinho, H. Susana; Real, Carla; Cyrne, Luísa
- Redox Biology, Vol. 2
The Parkinson's disease gene DJ-1 is also a key regulator of stroke-induced damage
journal, November 2007
- Aleyasin, H.; Rousseaux, M. W. C.; Phillips, M.
- Proceedings of the National Academy of Sciences, Vol. 104, Issue 47
The Protein Data Bank
journal, May 2002
- Berman, Helen M.; Battistuz, Tammy; Bhat, T. N.
- Acta Crystallographica Section D Biological Crystallography, Vol. 58, Issue 6
Works referencing / citing this record:
Molecular dynamics simulation of triclinic lysozyme in a crystal lattice: Molecular Dynamics of Crystal Lysozyme
journal, June 2015
- Janowski, Pawel A.; Liu, Chunmei; Deckman, Jason
- Protein Science, Vol. 25, Issue 1
X-ray radiation-induced addition of oxygen atoms to protein residues: Visualization of Oxidation and Peroxidation of Protein Residues
journal, July 2016
- Wang, Jimin
- Protein Science, Vol. 25, Issue 8
Very fast empirical prediction and rationalization of protein pKa values
journal, October 2005
- Li, Hui; Robertson, Andrew D.; Jensen, Jan H.
- Proteins: Structure, Function, and Bioinformatics, Vol. 61, Issue 4
DJ-1, a Novel Oncogene Which Transforms Mouse NIH3T3 Cells in Cooperation withras
journal, February 1997
- Nagakubo, Daisuke; Taira, Takahiro; Kitaura, Hirotake
- Biochemical and Biophysical Research Communications, Vol. 231, Issue 2
Intracellular metal binding and redox behavior of human DJ-1
journal, December 2017
- Barbieri, Letizia; Luchinat, Enrico; Banci, Lucia
- JBIC Journal of Biological Inorganic Chemistry, Vol. 23, Issue 1
DJ-1 as a human oncogene and potential therapeutic target
journal, February 2015
- Cao, Ji; Lou, Siyue; Ying, Meidan
- Biochemical Pharmacology, Vol. 93, Issue 3
Expanding the functional diversity of proteins through cysteine oxidation
journal, December 2008
- Reddie, Khalilah G.; Carroll, Kate S.
- Current Opinion in Chemical Biology, Vol. 12, Issue 6
Covalent targeting of acquired cysteines in cancer
journal, February 2016
- Visscher, Marieke; Arkin, Michelle R.; Dansen, Tobias B.
- Current Opinion in Chemical Biology, Vol. 30
Developing Irreversible Inhibitors of the Protein Kinase Cysteinome
journal, February 2013
- Liu, Qingsong; Sabnis, Yogesh; Zhao, Zheng
- Chemistry & Biology, Vol. 20, Issue 2
Molecular Basis for Redox Activation of Epidermal Growth Factor Receptor Kinase
journal, July 2016
- Truong, Thu H.; Ung, Peter Man-Un; Palde, Prakash B.
- Cell Chemical Biology, Vol. 23, Issue 7
Covalent inhibitors in drug discovery: from accidental discoveries to avoided liabilities and designed therapies
journal, September 2015
- Bauer, Renato A.
- Drug Discovery Today, Vol. 20, Issue 9
Absence of DJ-1 causes age-related retinal abnormalities in association with increased oxidative stress
journal, March 2017
- Bonilha, Vera L.; Bell, Brent A.; Rayborn, Mary E.
- Free Radical Biology and Medicine, Vol. 104
Geometric analysis characterizes molecular rigidity in generic and non-generic protein configurations
journal, October 2015
- Budday, Dominik; Leyendecker, Sigrid; van den Bedem, Henry
- Journal of the Mechanics and Physics of Solids, Vol. 83
Hydrogen peroxide sensing, signaling and regulation of transcription factors
journal, January 2014
- Marinho, H. Susana; Real, Carla; Cyrne, Luísa
- Redox Biology, Vol. 2
PTP1B: a double agent in metabolism and oncogenesis
journal, August 2010
- Yip, Shu-Chin; Saha, Sayanti; Chernoff, Jonathan
- Trends in Biochemical Sciences, Vol. 35, Issue 8
Radiolytic Modification of Sulfur-Containing Amino Acid Residues in Model Peptides: Fundamental Studies for Protein Footprinting
journal, April 2005
- Xu, Guozhong; Chance, Mark R.
- Analytical Chemistry, Vol. 77, Issue 8
Millisecond Radiolytic Modification of Peptides by Synchrotron X-rays Identified by Mass Spectrometry
journal, September 1999
- Maleknia, Simin D.; Brenowitz, Michael; Chance, Mark R.
- Analytical Chemistry, Vol. 71, Issue 18
Kinematic Flexibility Analysis: Hydrogen Bonding Patterns Impart a Spatial Hierarchy of Protein Motion
journal, September 2018
- Budday, Dominik; Leyendecker, Sigrid; van den Bedem, Henry
- Journal of Chemical Information and Modeling, Vol. 58, Issue 10
How Reactive are Druggable Cysteines in Protein Kinases?
journal, August 2018
- Awoonor-Williams, Ernest; Rowley, Christopher N.
- Journal of Chemical Information and Modeling, Vol. 58, Issue 9
Emerging and Re-Emerging Warheads for Targeted Covalent Inhibitors: Applications in Medicinal Chemistry and Chemical Biology
journal, December 2018
- Gehringer, Matthias; Laufer, Stefan A.
- Journal of Medicinal Chemistry, Vol. 62, Issue 12
qFit-ligand Reveals Widespread Conformational Heterogeneity of Drug-Like Molecules in X-Ray Electron Density Maps
journal, November 2018
- van Zundert, Gydo C. P.; Hudson, Brandi M.; de Oliveira, Saulo H. P.
- Journal of Medicinal Chemistry, Vol. 61, Issue 24
Identification of Cyanamide-Based Janus Kinase 3 (JAK3) Covalent Inhibitors
journal, November 2018
- Casimiro-Garcia, Agustin; Trujillo, John I.; Vajdos, Felix
- Journal of Medicinal Chemistry, Vol. 61, Issue 23
Preferred Hydrogen-Bonding Partners of Cysteine: Implications for Regulating Cys Functions
journal, September 2016
- Mazmanian, Karine; Sargsyan, Karen; Grauffel, Cédric
- The Journal of Physical Chemistry B, Vol. 120, Issue 39
Critical Assessment of the Strength of Hydrogen Bonds between the Sulfur Atom of Methionine/Cysteine and Backbone Amides in Proteins
journal, April 2015
- Mundlapati, V. Rao; Ghosh, Sanat; Bhattacherjee, Aditi
- The Journal of Physical Chemistry Letters, Vol. 6, Issue 8
Chemical Probe To Monitor the Parkinsonism-Associated Protein DJ-1 in Live Cells
journal, July 2018
- Drechsel, Jonas; Mandl, Franziska A.; Sieber, Stephan A.
- ACS Chemical Biology, Vol. 13, Issue 8
Discovery and Optimization of Inhibitors of the Parkinson’s Disease Associated Protein DJ-1
journal, July 2018
- Tashiro, Shinya; Caaveiro, Jose M. M.; Nakakido, Makoto
- ACS Chemical Biology, Vol. 13, Issue 9
Isocyanides and cyanides as natural products
journal, October 1992
- Scheuer, Paul J.
- Accounts of Chemical Research, Vol. 25, Issue 10
Reversible Cysteine Oxidation in Hydrogen Peroxide Sensing and Signal Transduction
journal, April 2014
- García-Santamarina, Sarela; Boronat, Susanna; Hidalgo, Elena
- Biochemistry, Vol. 53, Issue 16
Thermodynamic and Structural Characterization of the Specific Binding of Zn(II) to Human Protein DJ-1
journal, April 2014
- Tashiro, Shinya; Caaveiro, Jose M. M.; Wu, Chun-Xiang
- Biochemistry, Vol. 53, Issue 14
Cysteine p K a Depression by a Protonated Glutamic Acid in Human DJ-1 † ‡
journal, July 2008
- Witt, Anna C.; Lakshminarasimhan, Mahadevan; Remington, Benjamin C.
- Biochemistry, Vol. 47, Issue 28
Roles of Aspartic Acid-181 and Serine-222 in Intermediate Formation and Hydrolysis of the Mammalian Protein-Tyrosine-Phosphatase PTP1 †
journal, April 1997
- Lohse, Daniel L.; Denu, John M.; Santoro, Nicholas
- Biochemistry, Vol. 36, Issue 15
Rates of thiol-disulfide interchange reactions between mono- and dithiols and Ellman's reagent
journal, January 1977
- Whitesides, George M.; Lilburn, Jennifer E.; Szajewski, Richard P.
- The Journal of Organic Chemistry, Vol. 42, Issue 2
Redox regulation of protein tyrosine phosphatase 1B involves a sulphenyl-amide intermediate
journal, June 2003
- Salmeen, Annette; Andersen, Jannik N.; Myers, Michael P.
- Nature, Vol. 423, Issue 6941
Oxidation state of the active-site cysteine in protein tyrosine phosphatase 1B
journal, June 2003
- van Montfort, Rob L. M.; Congreve, Miles; Tisi, Dominic
- Nature, Vol. 423, Issue 6941
Intrinsic motions along an enzymatic reaction trajectory
journal, November 2007
- Henzler-Wildman, Katherine A.; Thai, Vu; Lei, Ming
- Nature, Vol. 450, Issue 7171
Oxidant stress evoked by pacemaking in dopaminergic neurons is attenuated by DJ-1
journal, November 2010
- Guzman, Jaime N.; Sanchez-Padilla, Javier; Wokosin, David
- Nature, Vol. 468, Issue 7324
K-Ras(G12C) inhibitors allosterically control GTP affinity and effector interactions
journal, November 2013
- Ostrem, Jonathan M.; Peters, Ulf; Sos, Martin L.
- Nature, Vol. 503, Issue 7477
Electric-field-stimulated protein mechanics
journal, December 2016
- Hekstra, Doeke R.; White, K. Ian; Socolich, Michael A.
- Nature, Vol. 540, Issue 7633
A proton relay enhances H2O2 sensitivity of GAPDH to facilitate metabolic adaptation
journal, January 2015
- Peralta, David; Bronowska, Agnieszka K.; Morgan, Bruce
- Nature Chemical Biology, Vol. 11, Issue 2
Reconciling the chemistry and biology of reactive oxygen species
journal, April 2008
- Winterbourn, Christine C.
- Nature Chemical Biology, Vol. 4, Issue 5
Automated identification of functional dynamic contact networks from X-ray crystallography
journal, August 2013
- van den Bedem, Henry; Bhabha, Gira; Yang, Kun
- Nature Methods, Vol. 10, Issue 9
Integrative, dynamic structural biology at atomic resolution—it's about time
journal, March 2015
- van den Bedem, Henry; Fraser, James S.
- Nature Methods, Vol. 12, Issue 4
Inside the human cancer tyrosine phosphatome
journal, December 2010
- Julien, Sofi G.; Dubé, Nadia; Hardy, Serge
- Nature Reviews Cancer, Vol. 11, Issue 1
Structural enzymology using X-ray free electron lasers
journal, December 2016
- Kupitz, Christopher; Olmos, Jose L.; Holl, Mark
- Structural Dynamics, Vol. 4, Issue 4
The Parkinson's disease protein DJ-1 is neuroprotective due to cysteine-sulfinic acid-driven mitochondrial localization
journal, June 2004
- Canet-Avilés, Rosa M.; Wilson, Mark A.; Miller, David W.
- Proceedings of the National Academy of Sciences, Vol. 101, Issue 24
The Parkinson's disease gene DJ-1 is also a key regulator of stroke-induced damage
journal, November 2007
- Aleyasin, H.; Rousseaux, M. W. C.; Phillips, M.
- Proceedings of the National Academy of Sciences, Vol. 104, Issue 47
Shoot-and-Trap: Use of specific x-ray damage to study structural protein dynamics by temperature-controlled cryo-crystallography
journal, August 2008
- Colletier, J. -P.; Bourgeois, D.; Sanson, B.
- Proceedings of the National Academy of Sciences, Vol. 105, Issue 33
Accessing protein conformational ensembles using room-temperature X-ray crystallography
journal, September 2011
- Fraser, J. S.; van den Bedem, H.; Samelson, A. J.
- Proceedings of the National Academy of Sciences, Vol. 108, Issue 39
The 1.1-A resolution crystal structure of DJ-1, the protein mutated in autosomal recessive early onset Parkinson's disease
journal, July 2003
- Wilson, M. A.; Collins, J. L.; Hod, Y.
- Proceedings of the National Academy of Sciences, Vol. 100, Issue 16
Predicting the X-ray lifetime of protein crystals
journal, December 2013
- Zeldin, O. B.; Brockhauser, S.; Bremridge, J.
- Proceedings of the National Academy of Sciences, Vol. 110, Issue 51
Conformational dynamics of a crystalline protein from microsecond-scale molecular dynamics simulations and diffuse X-ray scattering
journal, December 2014
- Wall, Michael E.; Van Benschoten, Andrew H.; Sauter, Nicholas K.
- Proceedings of the National Academy of Sciences, Vol. 111, Issue 50
Evolution of New Enzymatic Function by Structural Modulation of Cysteine Reactivity in Pseudomonas fluorescens Isocyanide Hydratase
journal, July 2010
- Lakshminarasimhan, Mahadevan; Madzelan, Peter; Nan, Ruth
- Journal of Biological Chemistry, Vol. 285, Issue 38
Parkinsonism-associated Protein DJ-1/Park7 Is a Major Protein Deglycase That Repairs Methylglyoxal- and Glyoxal-glycated Cysteine, Arginine, and Lysine Residues
journal, November 2014
- Richarme, Gilbert; Mihoub, Mouadh; Dairou, Julien
- Journal of Biological Chemistry, Vol. 290, Issue 3
Formation of a Stabilized Cysteine Sulfinic Acid Is Critical for the Mitochondrial Function of the Parkinsonism Protein DJ-1
journal, January 2009
- Blackinton, Jeff; Lakshminarasimhan, Mahadevan; Thomas, Kelly J.
- Journal of Biological Chemistry, Vol. 284, Issue 10
Understanding the p K a of Redox Cysteines: The Key Role of Hydrogen Bonding
journal, January 2013
- Roos, Goedele; Foloppe, Nicolas; Messens, Joris
- Antioxidants & Redox Signaling, Vol. 18, Issue 1
The Oxidation States of DJ-1 Dictate the Cell Fate in Response to Oxidative Stress Triggered by 4-HPR: Autophagy or Apoptosis?
journal, October 2014
- Cao, Ji; Ying, Meidan; Xie, Nan
- Antioxidants & Redox Signaling, Vol. 21, Issue 10
Protein Promiscuity in H 2 O 2 Signaling
journal, April 2019
- Young, David; Pedre, Brandan; Ezeriņa, Daria
- Antioxidants & Redox Signaling, Vol. 30, Issue 10
Human DJ-1 and its homologs are novel glyoxalases
journal, April 2012
- Lee, Ju-young; Song, Jeeyeon; Kwon, Kyu
- Human Molecular Genetics, Vol. 21, Issue 14
ROS-dependent regulation of Parkin and DJ-1 localization during oxidative stress in neurons
journal, August 2012
- Joselin, Alvin P.; Hewitt, Sarah J.; Callaghan, Steve M.
- Human Molecular Genetics, Vol. 21, Issue 22
Immunostaining of Oxidized DJ-1 in Human and Mouse Brains
journal, July 2014
- Saito, Yoshiro; Miyasaka, Tomohiro; Hatsuta, Hiroyuki
- Journal of Neuropathology & Experimental Neurology, Vol. 73, Issue 7
Modeling discrete heterogeneity in X-ray diffraction data by fitting multi-conformers
journal, September 2009
- van den Bedem, Henry; Dhanik, Ankur; Latombe, Jean-Claude
- Acta Crystallographica Section D Biological Crystallography, Vol. 65, Issue 10
Outrunning free radicals in room-temperature macromolecular crystallography
journal, June 2012
- Owen, Robin L.; Axford, Danny; Nettleship, Joanne E.
- Acta Crystallographica Section D Biological Crystallography, Vol. 68, Issue 7
X-ray-induced photo-chemistry and X-ray absorption spectroscopy of biological samples
journal, October 2012
- George, Graham N.; Pickering, Ingrid J.; Pushie, M. Jake
- Journal of Synchrotron Radiation, Vol. 19, Issue 6
RIDL : a tool to investigate radiation-induced density loss
journal, May 2018
- Bury, Charles Simon; Garman, Elspeth Frances
- Journal of Applied Crystallography, Vol. 51, Issue 3
Conformational variation of proteins at room temperature is not dominated by radiation damage
journal, January 2017
- Russi, Silvia; González, Ana; Kenner, Lillian R.
- Journal of Synchrotron Radiation, Vol. 24, Issue 1
Journey to the center of the protein: allostery from multitemperature multiconformer X-ray crystallography
journal, January 2019
- Keedy, Daniel A.
- Acta Crystallographica Section D Structural Biology, Vol. 75, Issue 2
DJ-1 deficiency in astrocytes selectively enhances mitochondrial Complex I inhibitor-induced neurotoxicity: Astrocyte DJ-1 loss enhances neurotoxicity
journal, January 2011
- Mullett, Steven J.; Hinkle, David A.
- Journal of Neurochemistry, Vol. 117, Issue 3
Protein tyrosine phosphatase structure-function relationships in regulation and pathogenesis: Protein tyrosine phosphatase structure-function
journal, July 2012
- Böhmer, Frank; Szedlacsek, Stefan; Tabernero, Lydia
- FEBS Journal, Vol. 280, Issue 2
Parkinson's disease-related DJ-1 modulates the expression of uncoupling protein 4 against oxidative stress
journal, April 2018
- Xu, Shaoqing; Yang, Xiaodong; Qian, Yiwei
- Journal of Neurochemistry, Vol. 145, Issue 4
Mutations in the DJ-1 Gene Associated with Autosomal Recessive Early-Onset Parkinsonism
journal, November 2002
- Bonifati, V.
- Science, Vol. 299, Issue 5604
Time-resolved serial crystallography captures high-resolution intermediates of photoactive yellow protein
journal, December 2014
- Tenboer, Jason; Basu, Shibom; Zatsepin, Nadia
- Science, Vol. 346, Issue 6214
The Catalytic Pathway of Cytochrome P450cam at Atomic Resolution
journal, March 2000
- Schlichting, I.
- Science, Vol. 287, Issue 5458
The role of dimer asymmetry and protomer dynamics in enzyme catalysis
journal, January 2017
- Kim, Tae Hun; Mehrabi, Pedram; Ren, Zhong
- Science, Vol. 355, Issue 6322
Biomolecular Simulation: A Computational Microscope for Molecular Biology
journal, June 2012
- Dror, Ron O.; Dirks, Robert M.; Grossman, J. P.
- Annual Review of Biophysics, Vol. 41, Issue 1
Pro-Survival Role for Parkinson's Associated Gene DJ-1 Revealed in Trophically Impaired Dopaminergic Neurons
journal, April 2010
- Aron, Liviu; Klein, Pontus; Pham, Thu-Trang
- PLoS Biology, Vol. 8, Issue 4
Protein Topology Determines Cysteine Oxidation Fate: The Case of Sulfenyl Amide Formation among Protein Families
journal, March 2015
- Defelipe, Lucas A.; Lanzarotti, Esteban; Gauto, Diego
- PLOS Computational Biology, Vol. 11, Issue 3
Exposing Hidden Alternative Backbone Conformations in X-ray Crystallography Using qFit
journal, October 2015
- Keedy, Daniel A.; Fraser, James S.; van den Bedem, Henry
- PLOS Computational Biology, Vol. 11, Issue 10
Mapping the conformational landscape of a dynamic enzyme by multitemperature and XFEL crystallography
journal, September 2015
- Keedy, Daniel A.; Kenner, Lillian R.; Warkentin, Matthew
- eLife, Vol. 4
X-ray radiation damage to biological samples: recent progress
journal, July 2019
- Garman, Elspeth F.; Weik, Martin
- Journal of Synchrotron Radiation, Vol. 26, Issue 4