PDBsum entry 1oes

Go to PDB code: 
protein metals links
Hydrolase PDB id
Protein chain
282 a.a. *
Waters ×195
* Residue conservation analysis
PDB id:
Name: Hydrolase
Title: Oxidation state of protein tyrosine phosphatase 1b
Structure: Protein-tyrosine phosphatase, non-receptor type 1. Chain: a. Fragment: catalytic domain, residues 1-321. Synonym: protein-tyrosine phosphatase 1b, ptp-1b. Engineered: yes. Other_details: covalent bond between the catalytic cys215 sg and ser216 n resulting in a novel sulfenylamide species
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 511693. Expression_system_variant: de3.
2.20Å     R-factor:   0.185     R-free:   0.233
Authors: R.L.M.Van Montfort,M.Congreve,D.Tisi,R.Carr,H.Jhoti
Key ref:
R.L.van Montfort et al. (2003). Oxidation state of the active-site cysteine in protein tyrosine phosphatase 1B. Nature, 423, 773-777. PubMed id: 12802339 DOI: 10.1038/nature01681
31-Mar-03     Release date:   12-Jun-03    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P18031  (PTN1_HUMAN) -  Tyrosine-protein phosphatase non-receptor type 1
435 a.a.
282 a.a.
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.  - Protein-tyrosine-phosphatase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Protein tyrosine phosphate + H2O = protein tyrosine + phosphate
Protein tyrosine phosphate
+ H(2)O
= protein tyrosine
+ phosphate
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     dephosphorylation   2 terms 
  Biochemical function     phosphatase activity     2 terms  


DOI no: 10.1038/nature01681 Nature 423:773-777 (2003)
PubMed id: 12802339  
Oxidation state of the active-site cysteine in protein tyrosine phosphatase 1B.
R.L.van Montfort, M.Congreve, D.Tisi, R.Carr, H.Jhoti.
Protein tyrosine phosphatases regulate signal transduction pathways involving tyrosine phosphorylation and have been implicated in the development of cancer, diabetes, rheumatoid arthritis and hypertension. Increasing evidence suggests that the cellular redox state is involved in regulating tyrosine phosphatase activity through the reversible oxidization of the catalytic cysteine to sulphenic acid (Cys-SOH). But how further oxidation to the irreversible sulphinic (Cys-SO2H) and sulphonic (Cys-SO3H) forms is prevented remains unclear. Here we report the crystal structures of the regulatory sulphenic and irreversible sulphinic and sulphonic acids of protein tyrosine phosphatase 1B (PTP1B), an important enzyme in the negative regulation of the insulin receptor and a therapeutic target in type II diabetes and obesity. We also identify a sulphenyl-amide species that is formed through oxidation of its catalytic cysteine. Formation of the sulphenyl-amide causes large changes in the PTP1B active site, which are reversible by reduction with the cellular reducing agent glutathione. The sulphenyl-amide is a protective intermediate in the oxidative inhibition of PTP1B. In addition, it may facilitate reactivation of PTP1B by biological thiols and signal a unique state of the protein.
  Selected figure(s)  
Figure 1.
Figure 1: Comparison of native and sulphenyl-amide PTP1B. a, Ribbon diagram of PTP1B. The phosphate-binding cradle is shown in red, the WPD loop in green and the pTyr recognition loop in gold. b, Superposition of native PTP1B (blue) and the sulphenyl-amide-containing structure (orange), showing different conformations of the pTyr recognition loop and the phosphate-binding cradle. c, Electron density of the catalytic cysteine and its neighbouring residues in reduced PTP1B (see Supplementary Information). d, Electron density of the newly identified sulphenyl-amide derivative of Cys 215. The electron density maps in c and d are contoured at 1 . All figures are generated using Aesop (M. Noble, Laboratory of Molecular Biophysics, University of Oxford, unpublished).
Figure 2.
Figure 2: Putative mechanism of sulphenyl-amide formation and subsequent reactivation. The catalytic cysteine of PTP1B (E -SH) is oxidized to a sulphenic acid (E -S -OH). The sulphenyl-amide may be formed by a direct mechanism involving a nucleophilic attack of the backbone nitrogen of Ser 216 on the S atom of Cys 215 and subsequent release of water. Alternatively, the sulphenic acid may be oxidized to a highly reactive intermediate by H[2]O[2] or an oxidized thiol, which then reacts to give the sulphenyl-amide. Reactivation of the enzyme occurs via mixed disulphide formation with a thiol. R, glutathione or DTT; X, leaving group OOH (sulphenoperoxoic acid) or OS(O)R (sulphinothioic acid).
  The above figures are reprinted by permission from Macmillan Publishers Ltd: Nature (2003, 423, 773-777) copyright 2003.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20626317 H.Antelmann, and J.D.Helmann (2011).
Thiol-based redox switches and gene regulation.
  Antioxid Redox Signal, 14, 1049-1063.  
21321730 K.P.Bhabak, B.J.Bhuyan, and G.Mugesh (2011).
Bioinorganic and medicinal chemistry: aspects of gold(i)-protein complexes.
  Dalton Trans, 40, 2099-2111.  
20177947 N.Nagahara (2011).
Intermolecular disulfide bond to modulate protein function as a redox-sensing switch.
  Amino Acids, 41, 59-72.  
20361350 A.Cuypers, M.Plusquin, T.Remans, M.Jozefczak, E.Keunen, H.Gielen, K.Opdenakker, A.R.Nair, E.Munters, T.J.Artois, T.Nawrot, J.Vangronsveld, and K.Smeets (2010).
Cadmium stress: an oxidative challenge.
  Biometals, 23, 927-940.  
20528774 A.E.Lane, J.T.Tan, C.L.Hawkins, A.K.Heather, and M.J.Davies (2010).
The myeloperoxidase-derived oxidant HOSCN inhibits protein tyrosine phosphatases and modulates cell signalling via the mitogen-activated protein kinase (MAPK) pathway in macrophages.
  Biochem J, 430, 161-169.  
20389282 A.Manford, T.Xia, A.K.Saxena, C.Stefan, F.Hu, S.D.Emr, and Y.Mao (2010).
Crystal structure of the yeast Sac1: implications for its phosphoinositide phosphatase function.
  EMBO J, 29, 1489-1498.
PDB code: 3lwt
19910238 B.C.Dickinson, D.Srikun, and C.J.Chang (2010).
Mitochondrial-targeted fluorescent probes for reactive oxygen species.
  Curr Opin Chem Biol, 14, 50-56.  
20482862 C.Brandsch, T.Schmidt, D.Behn, K.Weisse, A.S.Mueller, and G.I.Stangl (2010).
Glutathione deficiency down-regulates hepatic lipogenesis in rats.
  Lipids Health Dis, 9, 50.  
20724658 E.W.Miller, B.C.Dickinson, and C.J.Chang (2010).
Aquaporin-3 mediates hydrogen peroxide uptake to regulate downstream intracellular signaling.
  Proc Natl Acad Sci U S A, 107, 15681-15686.  
20716281 H.J.Forman (2010).
Reactive oxygen species and alpha,beta-unsaturated aldehydes as second messengers in signal transduction.
  Ann N Y Acad Sci, 1203, 35-44.  
19634988 M.A.Wouters, S.W.Fan, and N.L.Haworth (2010).
Disulfides as redox switches: from molecular mechanisms to functional significance.
  Antioxid Redox Signal, 12, 53-91.  
20231142 M.C.Villa-Abrille, C.I.Caldiz, I.L.Ennis, M.B.Nolly, M.J.Casarini, G.E.Chiappe de Cingolani, H.E.Cingolani, and N.G.Pérez (2010).
The Anrep effect requires transactivation of the epidermal growth factor receptor.
  J Physiol, 588, 1579-1590.  
20381358 S.C.Yip, S.Saha, and J.Chernoff (2010).
PTP1B: a double agent in metabolism and oncogenesis.
  Trends Biochem Sci, 35, 442-449.  
20015650 S.Sivaramakrishnan, A.H.Cummings, and K.S.Gates (2010).
Protection of a single-cysteine redox switch from oxidative destruction: On the functional role of sulfenyl amide formation in the redox-regulated enzyme PTP1B.
  Bioorg Med Chem Lett, 20, 444-447.  
21078955 Y.Diao, W.Liu, C.C.Wong, X.Wang, K.Lee, P.Y.Cheung, L.Pan, T.Xu, J.Han, J.R.Yates, M.Zhang, and Z.Wu (2010).
Oxidation-induced intramolecular disulfide bond inactivates mitogen-activated protein kinase kinase 6 by inhibiting ATP binding.
  Proc Natl Acad Sci U S A, 107, 20974-20979.  
19864455 Y.Xu, D.Baker, T.Quan, J.J.Baldassare, J.J.Voorhees, and G.J.Fisher (2010).
Receptor type protein tyrosine phosphatase-kappa mediates cross-talk between transforming growth factor-beta and epidermal growth factor receptor signaling pathways in human keratinocytes.
  Mol Biol Cell, 21, 29-35.  
19341304 A.L.Skinner, A.A.Vartia, T.D.Williams, and J.S.Laurence (2009).
Enzyme activity of phosphatase of regenerating liver is controlled by the redox environment and its C-terminal residues.
  Biochemistry, 48, 4262-4272.  
19712109 A.Trümpler, B.Schlott, P.Herrlich, P.A.Greer, and F.D.Böhmer (2009).
Calpain-mediated degradation of reversibly oxidized protein-tyrosine phosphatase 1B.
  FEBS J, 276, 5622-5633.  
19187004 D.F.Stowe, and A.K.Camara (2009).
Mitochondrial reactive oxygen species production in excitable cells: modulators of mitochondrial and cell function.
  Antioxid Redox Signal, 11, 1373-1414.  
19273857 D.J.Kemble, and G.Sun (2009).
Direct and specific inactivation of protein tyrosine kinases in the Src and FGFR families by reversible cysteine oxidation.
  Proc Natl Acad Sci U S A, 106, 5070-5075.  
19716756 D.Krishnamurthy, and A.M.Barrios (2009).
Profiling protein tyrosine phosphatase activity with mechanistic probes.
  Curr Opin Chem Biol, 13, 375-381.  
19591900 F.Chen, K.Beezhold, and V.Castranova (2009).
JNK1, a potential therapeutic target for hepatocellular carcinoma.
  Biochim Biophys Acta, 1796, 242-251.  
19099403 G.Saab-Rincón, and B.Valderrama (2009).
Protein engineering of redox-active enzymes.
  Antioxid Redox Signal, 11, 167-192.  
19507067 J.T.Hancock (2009).
The role of redox mechanisms in cell signalling.
  Mol Biotechnol, 43, 162-166.  
19607706 J.Witt, S.Barisic, E.Schumann, F.Allgöwer, O.Sawodny, T.Sauter, and D.Kulms (2009).
Mechanism of PP2A-mediated IKK beta dephosphorylation: a systems biological approach.
  BMC Syst Biol, 3, 71.  
19717737 M.Kurdi, and G.W.Booz (2009).
JAK redux: a second look at the regulation and role of JAKs in the heart.
  Am J Physiol Heart Circ Physiol, 297, H1545-H1556.  
18999917 N.Brandes, S.Schmitt, and U.Jakob (2009).
Thiol-based redox switches in eukaryotic proteins.
  Antioxid Redox Signal, 11, 997.  
19816407 S.H.Lim, S.K.Kwon, M.K.Lee, J.Moon, D.G.Jeong, E.Park, S.J.Kim, B.C.Park, S.C.Lee, S.E.Ryu, D.Y.Yu, B.H.Chung, E.Kim, P.K.Myung, and J.R.Lee (2009).
Synapse formation regulated by protein tyrosine phosphatase receptor T through interaction with cell adhesion molecules and Fyn.
  EMBO J, 28, 3564-3578.  
19371084 S.J.Tsai, U.Sen, L.Zhao, W.B.Greenleaf, J.Dasgupta, E.Fiorillo, V.Orrú, N.Bottini, and X.S.Chen (2009).
Crystal structure of the human lymphoid tyrosine phosphatase catalytic domain: insights into redox regulation .
  Biochemistry, 48, 4838-4845.
PDB code: 3h2x
19628032 W.Jeong, Y.Jung, H.Kim, S.J.Park, and S.G.Rhee (2009).
Thioredoxin-related protein 14, a new member of the thioredoxin family with disulfide reductase activity: implication in the redox regulation of TNF-alpha signaling.
  Free Radic Biol Med, 47, 1294-1303.  
18479206 A.Bindoli, J.M.Fukuto, and H.J.Forman (2008).
Thiol chemistry in peroxidase catalysis and redox signaling.
  Antioxid Redox Signal, 10, 1549-1564.  
18422654 A.Groen, J.Overvoorde, T.van der Wijk, and J.den Hertog (2008).
Redox regulation of dimerization of the receptor protein-tyrosine phosphatases RPTPalpha, LAR, RPTPmu and CD45.
  FEBS J, 275, 2597-2604.  
18164271 A.van der Vliet (2008).
NADPH oxidases in lung biology and pathology: host defense enzymes, and more.
  Free Radic Biol Med, 44, 938-955.  
18932179 B.K.Sarma, and G.Mugesh (2008).
Antioxidant activity of the anti-inflammatory compound ebselen: a reversible cyclization pathway via selenenic and seleninic acid intermediates.
  Chemistry, 14, 10603-10614.  
18544350 C.C.Winterbourn, and M.B.Hampton (2008).
Thiol chemistry and specificity in redox signaling.
  Free Radic Biol Med, 45, 549-561.  
18684987 D.P.Jones (2008).
Radical-free biology of oxidative stress.
  Am J Physiol Cell Physiol, 295, C849-C868.  
18227433 F.R.Salsbury, S.T.Knutson, L.B.Poole, and J.S.Fetrow (2008).
Functional site profiling and electrostatic analysis of cysteines modifiable to cysteine sulfenic acid.
  Protein Sci, 17, 299-312.  
18222094 F.Wang, S.Weidt, J.Xu, C.L.Mackay, P.R.Langridge-Smith, and P.J.Sadler (2008).
Identification of clusters from reactions of ruthenium arene anticancer complex with glutathione using nanoscale liquid chromatography Fourier transform ion cyclotron mass spectrometry combined with (18)O-labeling.
  J Am Soc Mass Spectrom, 19, 544-549.  
18602883 H.J.Forman, J.M.Fukuto, T.Miller, H.Zhang, A.Rinna, and S.Levy (2008).
The chemistry of cell signaling by reactive oxygen and nitrogen species and 4-hydroxynonenal.
  Arch Biochem Biophys, 477, 183-195.  
18725414 J.C.Lim, H.I.Choi, Y.S.Park, H.W.Nam, H.A.Woo, K.S.Kwon, Y.S.Kim, S.G.Rhee, K.Kim, and H.Z.Chae (2008).
Irreversible oxidation of the active-site cysteine of peroxiredoxin to cysteine sulfonic acid for enhanced molecular chaperone activity.
  J Biol Chem, 283, 28873-28880.  
18774901 J.J.Mieyal, M.M.Gallogly, S.Qanungo, E.A.Sabens, and M.D.Shelton (2008).
Molecular mechanisms and clinical implications of reversible protein S-glutathionylation.
  Antioxid Redox Signal, 10, 1941-1988.  
18298791 J.den Hertog, A.Ostman, and F.D.Böhmer (2008).
Protein tyrosine phosphatases: regulatory mechanisms.
  FEBS J, 275, 831-847.  
18573911 K.Chen, M.T.Kirber, H.Xiao, Y.Yang, and J.F.Keaney (2008).
Regulation of ROS signal transduction by NADPH oxidase 4 localization.
  J Cell Biol, 181, 1129-1139.  
18493649 K.G.Reddie, Y.H.Seo, W.B.Muse Iii, S.E.Leonard, and K.S.Carroll (2008).
A chemical approach for detecting sulfenic acid-modified proteins in living cells.
  Mol Biosyst, 4, 521-531.  
18500784 K.Keerthi, S.Sivaramakrishnan, and K.S.Gates (2008).
Evidence for a Morin type intramolecular cyclization of an alkene with a phenylsulfenic acid group in neutral aqueous solution.
  Chem Res Toxicol, 21, 1368-1374.  
18234830 K.Kubiak, and W.Nowak (2008).
Molecular dynamics simulations of the photoactive protein nitrile hydratase.
  Biophys J, 94, 3824-3838.  
18852458 K.Ratia, S.Pegan, J.Takayama, K.Sleeman, M.Coughlin, S.Baliji, R.Chaudhuri, W.Fu, B.S.Prabhakar, M.E.Johnson, S.C.Baker, A.K.Ghosh, and A.D.Mesecar (2008).
A noncovalent class of papain-like protease/deubiquitinase inhibitors blocks SARS virus replication.
  Proc Natl Acad Sci U S A, 105, 16119-16124.  
18778410 L.Chen, R.Na, M.Gu, A.B.Salmon, Y.Liu, H.Liang, W.Qi, H.Van Remmen, A.Richardson, and Q.Ran (2008).
Reduction of mitochondrial H2O2 by overexpressing peroxiredoxin 3 improves glucose tolerance in mice.
  Aging Cell, 7, 866-878.  
18298793 L.Tabernero, A.R.Aricescu, E.Y.Jones, and S.E.Szedlacsek (2008).
Protein tyrosine phosphatases: structure-function relationships.
  FEBS J, 275, 867-882.  
18444899 N.Rouhier, S.D.Lemaire, and J.P.Jacquot (2008).
The role of glutathione in photosynthetic organisms: emerging functions for glutaredoxins and glutathionylation.
  Annu Rev Plant Biol, 59, 143-166.  
18280234 P.Herrlich, M.Karin, and C.Weiss (2008).
Supreme EnLIGHTenment: damage recognition and signaling in the mammalian UV response.
  Mol Cell, 29, 279-290.  
18957266 P.Sharma, R.Chakraborty, L.Wang, B.Min, M.L.Tremblay, T.Kawahara, J.D.Lambeth, and S.J.Haque (2008).
Redox regulation of interleukin-4 signaling.
  Immunity, 29, 551-564.  
18573100 R.J.Gruninger, L.Brent Selinger, and S.C.Mosimann (2008).
Effect of ionic strength and oxidation on the P-loop conformation of the protein tyrosine phosphatase-like phytase, PhyAsr.
  FEBS J, 275, 3783-3792.
PDB codes: 2psz 2pt0 3d1h 3d1o 3d1q
18595691 S.Bhattacharya, J.N.Labutti, D.R.Seiner, and K.S.Gates (2008).
Oxidative inactivation of protein tyrosine phosphatase 1B by organic hydroperoxides.
  Bioorg Med Chem Lett, 18, 5856-5859.  
18545666 S.Galli, V.G.Antico Arciuch, C.Poderoso, D.P.Converso, Q.Zhou, E.Bal de Kier Joffé, E.Cadenas, J.Boczkowski, M.C.Carreras, and J.J.Poderoso (2008).
Tumor cell phenotype is sustained by selective MAPK oxidation in mitochondria.
  PLoS ONE, 3, e2379.  
18707220 S.R.Thomas, P.K.Witting, and G.R.Drummond (2008).
Redox control of endothelial function and dysfunction: molecular mechanisms and therapeutic opportunities.
  Antioxid Redox Signal, 10, 1713-1765.  
18363800 S.Soonsanga, J.W.Lee, and J.D.Helmann (2008).
Oxidant-dependent switching between reversible and sacrificial oxidation pathways for Bacillus subtilis OhrR.
  Mol Microbiol, 68, 978-986.  
18436649 T.Nakamura, T.Yamamoto, M.Abe, H.Matsumura, Y.Hagihara, T.Goto, T.Yamaguchi, and T.Inoue (2008).
Oxidation of archaeal peroxiredoxin involves a hypervalent sulfur intermediate.
  Proc Natl Acad Sci U S A, 105, 6238-6242.
PDB codes: 2e2g 2e2m 2nvl 2zct
18796006 T.Shibata, H.Nakahara, N.Kita, Y.Matsubara, C.Han, Y.Morimitsu, N.Iwamoto, Y.Kumagai, M.Nishida, H.Kurose, N.Aoki, M.Ojika, and K.Uchida (2008).
A food-derived synergist of NGF signaling: identification of protein tyrosine phosphatase 1B as a key regulator of NGF receptor-initiated signal transduction.
  J Neurochem, 107, 1248-1260.  
18840608 Y.Y.Chen, H.M.Chu, K.T.Pan, C.H.Teng, D.L.Wang, A.H.Wang, K.H.Khoo, and T.C.Meng (2008).
Cysteine S-Nitrosylation Protects Protein-tyrosine Phosphatase 1B against Oxidation-induced Permanent Inactivation.
  J Biol Chem, 283, 35265-35272.
PDB code: 3eu0
17567745 A.A.Puhl, R.J.Gruninger, R.Greiner, T.W.Janzen, S.C.Mosimann, and L.B.Selinger (2007).
Kinetic and structural analysis of a bacterial protein tyrosine phosphatase-like myo-inositol polyphosphatase.
  Protein Sci, 16, 1368-1378.
PDB codes: 2b4o 2b4p 2b4u
17848967 B.D'Autréaux, and M.B.Toledano (2007).
ROS as signalling molecules: mechanisms that generate specificity in ROS homeostasis.
  Nat Rev Mol Cell Biol, 8, 813-824.  
17434122 E.A.Veal, A.M.Day, and B.A.Morgan (2007).
Hydrogen peroxide sensing and signaling.
  Mol Cell, 26, 1.  
17331952 G.Wang, C.Strang, P.J.Pfaffinger, and M.Covarrubias (2007).
Zn2+-dependent redox switch in the intracellular T1-T1 interface of a Kv channel.
  J Biol Chem, 282, 13637-13647.  
17349920 H.J.Forman (2007).
Use and abuse of exogenous H2O2 in studies of signal transduction.
  Free Radic Biol Med, 42, 926-932.  
17462910 H.Lioe, and R.A.O'Hair (2007).
A novel salt bridge mechanism highlights the need for nonmobile proton conditions to promote disulfide bond cleavage in protonated peptides under low-energy collisional activation.
  J Am Soc Mass Spectrom, 18, 1109-1123.  
17561098 I.Weibrecht, S.A.Böhmer, M.Dagnell, K.Kappert, A.Ostman, and F.D.Böhmer (2007).
Oxidation sensitivity of the catalytic cysteine of the protein-tyrosine phosphatases SHP-1 and SHP-2.
  Free Radic Biol Med, 43, 100-110.  
17502599 J.W.Lee, S.Soonsanga, and J.D.Helmann (2007).
A complex thiolate switch regulates the Bacillus subtilis organic peroxide sensor OhrR.
  Proc Natl Acad Sci U S A, 104, 8743-8748.  
17280484 L.C.Hool, and B.Corry (2007).
Redox control of calcium channels: from mechanisms to therapeutic opportunities.
  Antioxid Redox Signal, 9, 409-435.  
17115885 P.Chiarugi, and F.Buricchi (2007).
Protein tyrosine phosphorylation and reversible oxidation: two cross-talking posttranslation modifications.
  Antioxid Redox Signal, 9, 1.  
17061035 S.Carballal, B.Alvarez, L.Turell, H.Botti, B.A.Freeman, and R.Radi (2007).
Sulfenic acid in human serum albumin.
  Amino Acids, 32, 543-551.  
17115887 S.W.Ryter, H.P.Kim, A.Hoetzel, J.W.Park, K.Nakahira, X.Wang, and A.M.Choi (2007).
Mechanisms of cell death in oxidative stress.
  Antioxid Redox Signal, 9, 49-89.  
17604642 V.Shetty, D.S.Spellman, and T.A.Neubert (2007).
Characterization by tandem mass spectrometry of stable cysteine sulfenic acid in a cysteine switch peptide of matrix metalloproteinases.
  J Am Soc Mass Spectrom, 18, 1544-1551.  
17567240 Y.Funato, and H.Miki (2007).
Nucleoredoxin, a novel thioredoxin family member involved in cell growth and differentiation.
  Antioxid Redox Signal, 9, 1035-1057.  
16987029 A.Pitzschke, C.Forzani, and H.Hirt (2006).
Reactive oxygen species signaling in plants.
  Antioxid Redox Signal, 8, 1757-1764.  
16781456 A.Rinna, M.Torres, and H.J.Forman (2006).
Stimulation of the alveolar macrophage respiratory burst by ADP causes selective glutathionylation of protein tyrosine phosphatase 1B.
  Free Radic Biol Med, 41, 86-91.  
16337878 A.V.Peskin, and C.C.Winterbourn (2006).
Taurine chloramine is more selective than hypochlorous acid at targeting critical cysteines and inactivating creatine kinase and glyceraldehyde-3-phosphate dehydrogenase.
  Free Radic Biol Med, 40, 45-53.  
17043136 B.Szöor, J.Wilson, H.McElhinney, L.Tabernero, and K.R.Matthews (2006).
Protein tyrosine phosphatase TbPTP1: A molecular switch controlling life cycle differentiation in trypanosomes.
  J Cell Biol, 175, 293-303.  
17081111 C.Jacob, I.Knight, and P.G.Winyard (2006).
Aspects of the biological redox chemistry of cysteine: from simple redox responses to sophisticated signalling pathways.
  Biol Chem, 387, 1385-1397.  
17081112 C.von Montfort, V.S.Sharov, S.Metzger, C.Schöneich, H.Sies, and L.O.Klotz (2006).
Singlet oxygen inactivates protein tyrosine phosphatase-1B by oxidation of the active site cysteine.
  Biol Chem, 387, 1399-1404.  
16677071 J.R.Stone, and S.Yang (2006).
Hydrogen peroxide: a signaling messenger.
  Antioxid Redox Signal, 8, 243-270.  
16987034 J.V.Cross, and D.J.Templeton (2006).
Regulation of signal transduction through protein cysteine oxidation.
  Antioxid Redox Signal, 8, 1819-1827.  
16567803 K.Kaiserova, S.Srivastava, J.D.Hoetker, S.O.Awe, X.L.Tang, J.Cai, and A.Bhatnagar (2006).
Redox activation of aldose reductase in the ischemic heart.
  J Biol Chem, 281, 15110-15120.  
16445714 L.C.Hool (2006).
Reactive oxygen species in cardiac signalling: from mitochondria to plasma membrane ion channels.
  Clin Exp Pharmacol Physiol, 33, 146-151.  
16893901 M.Kanda, Y.Ihara, H.Murata, Y.Urata, T.Kono, J.Yodoi, S.Seto, K.Yano, and T.Kondo (2006).
Glutaredoxin modulates platelet-derived growth factor-dependent cell signaling by regulating the redox status of low molecular weight protein-tyrosine phosphatase.
  J Biol Chem, 281, 28518-28528.  
17057753 N.K.Tonks (2006).
Protein tyrosine phosphatases: from genes, to function, to disease.
  Nat Rev Mol Cell Biol, 7, 833-846.  
16369939 N.W.Blackstone (2006).
Multicellular redox regulation: integrating organismal biology and redox chemistry.
  Bioessays, 28, 72-77.  
16278309 R.Gupta, S.Karpatkin, and R.S.Basch (2006).
Hematopoiesis and stem cell renewal in long-term bone marrow cultures containing catalase.
  Blood, 107, 1837-1846.  
16607115 W.Dröge (2006).
Redox regulation in anabolic and catabolic processes.
  Curr Opin Clin Nutr Metab Care, 9, 190-195.  
16797630 Y.Chen, M.Yu, D.P.Jones, J.T.Greenamyre, and J.Cai (2006).
Protection against oxidant-induced apoptosis by mitochondrial thioredoxin in SH-SY5Y neuroblastoma cells.
  Toxicol Appl Pharmacol, 216, 256-262.  
16849327 Y.Xu, Y.Shao, J.J.Voorhees, and G.J.Fisher (2006).
Oxidative inhibition of receptor-type protein-tyrosine phosphatase kappa by ultraviolet irradiation activates epidermal growth factor receptor in human keratinocytes.
  J Biol Chem, 281, 27389-27397.  
15843166 A.Barthel, and L.O.Klotz (2005).
Phosphoinositide 3-kinase signaling in the cellular response to oxidative stress.
  Biol Chem, 386, 207-216.  
15623519 A.Groen, S.Lemeer, T.van der Wijk, J.Overvoorde, A.J.Heck, A.Ostman, D.Barford, M.Slijper, and J.den Hertog (2005).
Differential oxidation of protein-tyrosine phosphatases.
  J Biol Chem, 280, 10298-10304.  
15787978 A.S.Müller, E.Most, and J.Pallauf (2005).
Effects of a supranutritional dose of selenate compared with selenite on insulin sensitivity in type II diabetic dbdb mice.
  J Anim Physiol Anim Nutr (Berl), 89, 94.  
15890001 A.Salmeen, and D.Barford (2005).
Functions and mechanisms of redox regulation of cysteine-based phosphatases.
  Antioxid Redox Signal, 7, 560-577.  
15677487 B.J.Goldstein, K.Mahadev, M.Kalyankar, and X.Wu (2005).
Redox paradox: insulin action is facilitated by insulin-stimulated reactive oxygen species with multiple potential signaling targets.
  Diabetes, 54, 311-321.  
15998257 B.J.Goldstein, K.Mahadev, X.Wu, L.Zhu, and H.Motoshima (2005).
Role of insulin-induced reactive oxygen species in the insulin signaling pathway.
  Antioxid Redox Signal, 7, 1021-1031.  
16306267 C.E.McCartney, H.McClafferty, J.M.Huibant, E.G.Rowan, M.J.Shipston, and I.C.Rowe (2005).
A cysteine-rich motif confers hypoxia sensitivity to mammalian large conductance voltage- and Ca-activated K (BK) channel alpha-subunits.
  Proc Natl Acad Sci U S A, 102, 17870-17876.  
16271885 C.Grundner, H.L.Ng, and T.Alber (2005).
Mycobacterium tuberculosis protein tyrosine phosphatase PtpB structure reveals a diverged fold and a buried active site.
  Structure, 13, 1625-1634.
PDB code: 1ywf
15579467 D.J.Levinthal, and D.B.Defranco (2005).
Reversible oxidation of ERK-directed protein phosphatases drives oxidative toxicity in neurons.
  J Biol Chem, 280, 5875-5883.  
15570599 D.Luo, S.W.Smith, and B.D.Anderson (2005).
Kinetics and mechanism of the reaction of cysteine and hydrogen peroxide in aqueous solution.
  J Pharm Sci, 94, 304-316.  
16158225 H.Haase, and W.Maret (2005).
Protein tyrosine phosphatases as targets of the combined insulinomimetic effects of zinc and oxidants.
  Biometals, 18, 333-338.  
15766528 H.Kamata, S.Honda, S.Maeda, L.Chang, H.Hirata, and M.Karin (2005).
Reactive oxygen species promote TNFalpha-induced death and sustained JNK activation by inhibiting MAP kinase phosphatases.
  Cell, 120, 649-661.  
15389864 I.Dalle-Donne, A.Scaloni, D.Giustarini, E.Cavarra, G.Tell, G.Lungarella, R.Colombo, R.Rossi, and A.Milzani (2005).
Proteins as biomarkers of oxidative/nitrosative stress in diseases: the contribution of redox proteomics.
  Mass Spectrom Rev, 24, 55-99.  
15650395 I.Rahman, S.K.Biswas, L.A.Jimenez, M.Torres, and H.J.Forman (2005).
Glutathione, stress responses, and redox signaling in lung inflammation.
  Antioxid Redox Signal, 7, 42-59.  
15933714 J.Kwon, C.K.Qu, J.S.Maeng, R.Falahati, C.Lee, and M.S.Williams (2005).
Receptor-stimulated oxidation of SHP-2 promotes T-cell adhesion through SLP-76-ADAP.
  EMBO J, 24, 2331-2341.  
15998259 J.L.Evans, B.A.Maddux, and I.D.Goldfine (2005).
The molecular basis for oxidative stress-induced insulin resistance.
  Antioxid Redox Signal, 7, 1040-1052.  
16200195 J.L.Luo, H.Kamata, and M.Karin (2005).
IKK/NF-kappaB signaling: balancing life and death--a new approach to cancer therapy.
  J Clin Invest, 115, 2625-2632.  
16380818 J.L.Luo, H.Kamata, and M.Karin (2005).
The anti-death machinery in IKK/NF-kappaB signaling.
  J Clin Immunol, 25, 541-550.  
15890022 J.Rudolph (2005).
Redox regulation of the Cdc25 phosphatases.
  Antioxid Redox Signal, 7, 761-767.  
15890002 P.Chiarugi, and E.Giannoni (2005).
Anchorage-dependent cell growth: tyrosine kinases and phosphatases meet redox regulation.
  Antioxid Redox Signal, 7, 578-592.  
16317705 P.Dent, Y.Fang, S.Gupta, E.Studer, C.Mitchell, S.Spiegel, and P.B.Hylemon (2005).
Conjugated bile acids promote ERK1/2 and AKT activation via a pertussis toxin-sensitive mechanism in murine and human hepatocytes.
  Hepatology, 42, 1291-1299.  
15998249 R.E.Shackelford, A.N.Heinloth, S.C.Heard, and R.S.Paules (2005).
Cellular and molecular targets of protein S-glutathiolation.
  Antioxid Redox Signal, 7, 940-950.  
15780595 S.G.Rhee, S.W.Kang, W.Jeong, T.S.Chang, K.S.Yang, and H.A.Woo (2005).
Intracellular messenger function of hydrogen peroxide and its regulation by peroxiredoxins.
  Curr Opin Cell Biol, 17, 183-189.  
15998263 S.J.Salsman, K.Hensley, and R.A.Floyd (2005).
Sensitivity of protein tyrosine phosphatase activity to the redox environment, cytochrome C, and microperoxidase.
  Antioxid Redox Signal, 7, 1078-1088.  
15630428 T.Mustelin, T.Vang, and N.Bottini (2005).
Protein tyrosine phosphatases and the immune response.
  Nat Rev Immunol, 5, 43-57.  
15998262 W.Dröge (2005).
Oxidative enhancement of insulin receptor signaling: experimental findings and clinical implications.
  Antioxid Redox Signal, 7, 1071-1077.  
15778445 Y.Li, W.P.Yu, C.W.Lin, and T.Y.Chen (2005).
Oxidation and reduction control of the inactivation gating of Torpedo ClC-0 chloride channels.
  Biophys J, 88, 3936-3945.  
15134754 C.Laloi, K.Apel, and A.Danon (2004).
Reactive oxygen signalling: the latest news.
  Curr Opin Plant Biol, 7, 323-328.  
14762163 C.Persson, T.Sjöblom, A.Groen, K.Kappert, U.Engström, U.Hellman, C.H.Heldin, J.den Hertog, and A.Ostman (2004).
Preferential oxidation of the second phosphatase domain of receptor-like PTP-alpha revealed by an antibody against oxidized protein tyrosine phosphatases.
  Proc Natl Acad Sci U S A, 101, 1886-1891.  
14704153 G.Kozlov, J.Cheng, E.Ziomek, D.Banville, K.Gehring, and I.Ekiel (2004).
Structural insights into molecular function of the metastasis-associated phosphatase PRL-3.
  J Biol Chem, 279, 11882-11889.
PDB code: 1r6h
15024017 I.K.Lund, H.S.Andersen, L.F.Iversen, O.H.Olsen, K.B.Møller, A.K.Pedersen, Y.Ge, D.D.Holsworth, M.J.Newman, F.U.Axe, and N.P.Møller (2004).
Structure-based design of selective and potent inhibitors of protein-tyrosine phosphatase beta.
  J Biol Chem, 279, 24226-24235.  
15151929 J.Seligman, Y.Zipser, and N.S.Kosower (2004).
Tyrosine phosphorylation, thiol status, and protein tyrosine phosphatase in rat epididymal spermatozoa.
  Biol Reprod, 71, 1009-1015.  
15352167 J.V.Cross, and D.J.Templeton (2004).
Thiol oxidation of cell signaling proteins: Controlling an apoptotic equilibrium.
  J Cell Biochem, 93, 104-111.  
15377225 K.Apel, and H.Hirt (2004).
Reactive oxygen species: metabolism, oxidative stress, and signal transduction.
  Annu Rev Plant Biol, 55, 373-399.  
14744249 L.B.Poole, P.A.Karplus, and A.Claiborne (2004).
Protein sulfenic acids in redox signaling.
  Annu Rev Pharmacol Toxicol, 44, 325-347.  
15110387 O.Augusto, M.G.Bonini, and D.Trindade (2004).
Spin trapping of glutathiyl and protein radicals produced from nitric oxide-derived oxidants.
  Free Radic Biol Med, 36, 1224-1232.  
15247926 P.Gulati, B.Markova, M.Göttlicher, F.D.Böhmer, and P.A.Herrlich (2004).
UVA inactivates protein tyrosine phosphatases by calpain-mediated degradation.
  EMBO Rep, 5, 812-817.  
15352154 R.B.Ferraro, J.L.Sousa, R.D.Cunha, and J.R.Meyer-Fernandes (2004).
Characterization of an ecto-phosphatase activity in malpighian tubules of hematophagous bug Rhodnius prolixus.
  Arch Insect Biochem Physiol, 57, 40-49.  
15294898 T.van der Wijk, J.Overvoorde, and J.den Hertog (2004).
H2O2-induced intermolecular disulfide bond formation between receptor protein-tyrosine phosphatases.
  J Biol Chem, 279, 44355-44361.  
14670964 X.Fu, J.L.Kao, C.Bergt, S.Y.Kassim, N.P.Huq, A.d'Avignon, W.C.Parks, R.P.Mecham, and J.W.Heinecke (2004).
Oxidative cross-linking of tryptophan to glycine restrains matrix metalloproteinase activity: specific structural motifs control protein oxidation.
  J Biol Chem, 279, 6209-6212.  
15382121 Y.Fang, S.I.Han, C.Mitchell, S.Gupta, E.Studer, S.Grant, P.B.Hylemon, and P.Dent (2004).
Bile acids induce mitochondrial ROS, which promote activation of receptor tyrosine kinases and signaling pathways in rat hepatocytes.
  Hepatology, 40, 961-971.  
14504278 Q.Wang, G.R.Pfeiffer, and W.A.Gaarde (2003).
Activation of SRC tyrosine kinases in response to ICAM-1 ligation in pulmonary microvascular endothelial cells.
  J Biol Chem, 278, 47731-47743.  
12923527 R.Wetzker, and F.D.Böhmer (2003).
Transactivation joins multiple tracks to the ERK/MAPK cascade.
  Nat Rev Mol Cell Biol, 4, 651-657.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.