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PDBsum entry 2j16

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protein ligands metals Protein-protein interface(s) links
Hydrolase PDB id
2j16
Jmol
Contents
Protein chains
134 a.a. *
144 a.a. *
Ligands
SO4 ×3
Metals
_MG
Waters ×41
* Residue conservation analysis
PDB id:
2j16
Name: Hydrolase
Title: Apo & sulphate bound forms of sdp-1
Structure: Tyrosine-protein phosphatase yil113w. Chain: a. Fragment: residues 17-198. Synonym: sdp-1. Engineered: yes. Tyrosine-protein phosphatase yil113w. Chain: b. Fragment: residues 17-198. Synonym: sdp-1.
Source: Saccharomyces cerevisiae. Baker's yeast. Organism_taxid: 4932. Strain: s288c / ab972. Expressed in: escherichia coli. Expression_system_taxid: 562. Expression_system_variant: plyss.
Resolution:
2.70Å     R-factor:   0.232     R-free:   0.257
Authors: D.C.Briggs,N.Q.Mcdonald
Key ref:
G.C.Fox et al. (2007). Redox-mediated substrate recognition by Sdp1 defines a new group of tyrosine phosphatases. Nature, 447, 487-492. PubMed id: 17495930 DOI: 10.1038/nature05804
Date:
09-Aug-06     Release date:   22-May-07    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P40479  (SDP1_YEAST) -  Dual-specificity protein phosphatase SDP1
Seq:
Struc:
209 a.a.
134 a.a.*
Protein chain
Pfam   ArchSchema ?
P40479  (SDP1_YEAST) -  Dual-specificity protein phosphatase SDP1
Seq:
Struc:
209 a.a.
144 a.a.
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Enzyme reactions 
   Enzyme class: Chains A, B: E.C.3.1.3.48  - 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     3 terms  

 

 
    reference    
 
 
DOI no: 10.1038/nature05804 Nature 447:487-492 (2007)
PubMed id: 17495930  
 
 
Redox-mediated substrate recognition by Sdp1 defines a new group of tyrosine phosphatases.
G.C.Fox, M.Shafiq, D.C.Briggs, P.P.Knowles, M.Collister, M.J.Didmon, V.Makrantoni, R.J.Dickinson, S.Hanrahan, N.Totty, M.J.Stark, S.M.Keyse, N.Q.McDonald.
 
  ABSTRACT  
 
Reactive oxygen species trigger cellular responses by activation of stress-responsive mitogen-activated protein kinase (MAPK) signalling pathways. Reversal of MAPK activation requires the transcriptional induction of specialized cysteine-based phosphatases that mediate MAPK dephosphorylation. Paradoxically, oxidative stresses generally inactivate cysteine-based phosphatases by thiol modification and thus could lead to sustained or uncontrolled MAPK activation. Here we describe how the stress-inducible MAPK phosphatase, Sdp1, presents an unusual solution to this apparent paradox by acquiring enhanced catalytic activity under oxidative conditions. Structural and biochemical evidence reveals that Sdp1 employs an intramolecular disulphide bridge and an invariant histidine side chain to selectively recognize a tyrosine-phosphorylated MAPK substrate. Optimal activity critically requires the disulphide bridge, and thus, to the best of our knowledge, Sdp1 is the first example of a cysteine-dependent phosphatase that couples oxidative stress with substrate recognition. We show that Sdp1, and its paralogue Msg5, have similar properties and belong to a new group of phosphatases unique to yeast and fungal taxa.
 
  Selected figure(s)  
 
Figure 1.
Figure 1: Sdp1 activity is sensitive to reducing agents. a, Effect of DTT on the Sdp1 kinetic constants for pNPP hydrolysis. Solid lines indicate fit to the Michaelis–Menten equation. Tabulated rate constants and s.e.m. for Sdp1 and VHR are also shown. Catalytic efficiency is defined as k[cat]/K[m]. Sdp1 is used to indicate a truncated form of Sdp1 (residues 17 to 197) used for structural and biochemical work as well as for the Sdp1 point mutants. Full-length Sdp1, indicated by Sdp1(FL), gave equivalent kinetic constants for both wild-type and mutant proteins. b, Time course of recombinant activated (diphosphorylated) ERK2 dephosphorylation by Sdp1 in the presence (right panel) or absence (left panel) of reducing agent, detected using phosphothreonine (pT) or phosphotyrosine (pY) specific antibodies by western blot analysis. c, Upper panel shows activated ERK2 dephosphorylation after a two-hour incubation with Sdp1 (no DTT) or the dual-specific DUSP6/MKP-3 and the tyrosine-specific VHR (both with 1 mM DTT). A truncated Sdp1 (residues 56–197) and a catalytically dead Sdp1(C140S) mutant were also tested without DTT. Lower panel shows a schematic for Sdp1, indicating the position of cysteine residues, and demarcates the catalytic CBP domain in green. d, Upper panel, activity of a series of N-terminal Sdp1 deletion mutants towards phospho-ERK2 by western blot, as previously described. Lower panel, same series of mutants and their activity towards pNPP.
Figure 3.
Figure 3: Phosphotyrosine recognition by His 111 and the Cys 47–Cys 142 disulphide bridge. a, Left panel shows substrate-induced conformational changes in the Sdp1 active site. Apo (pink), sulphate- (gold) and phosphotyrosine-bound (blue) Sdp1. Right panel shows a superposition of Sdp (phosphotyrosine-bound) and VHR (magenta), indicating His 111 is structurally equivalent to aspartic acid 92 of VHR. b, Stereoview of a SIGMAA-weighted (2F[o]–F[c]) electron density map contoured at 1 close to the Sdp1 active site, highlighting density for the His 111 side chain and Cys 47–Cys 142 disulphide bridge. The phosphotyrosine ring is shown in green and red, mainchain atoms for phosphotyrosine omitted from the refined model are shown in grey. c, Surface representation of the active sites of Sdp1, VHR and PTP1B with phosphotyrosine substrates, and equivalent phosphotyrosine contact residues, identified.
 
  The above figures are reprinted by permission from Macmillan Publishers Ltd: Nature (2007, 447, 487-492) copyright 2007.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21409566 C.Romá-Mateo, A.Sacristán-Reviriego, N.J.Beresford, J.A.Caparrós-Martín, F.A.Culiáñez-Macià, H.Martín, M.Molina, L.Tabernero, and R.Pulido (2011).
Phylogenetic and genetic linkage between novel atypical dual-specificity phosphatases from non-metazoan organisms.
  Mol Genet Genomics, 285, 341-354.  
19618296 F.M.Squina, J.Leal, V.T.Cipriano, N.M.Martinez-Rossi, and A.Rossi (2010).
Transcription of the Neurospora crassa 70-kDa class heat shock protein genes is modulated in response to extracellular pH changes.
  Cell Stress Chaperones, 15, 225-231.  
20653956 G.Porcu, C.Wilson, D.Di Giandomenico, and A.Ragnini-Wilson (2010).
A yeast-based genomic strategy highlights the cell protein networks altered by FTase inhibitor peptidomimetics.
  Mol Cancer, 9, 197.  
19567874 C.A.Bonham, and P.O.Vacratsis (2009).
Redox regulation of the human dual specificity phosphatase YVH1 through disulfide bond formation.
  J Biol Chem, 284, 22853-22864.  
19152646 C.K.Sen (2009).
Wound healing essentials: let there be oxygen.
  Wound Repair Regen, 17, 1.  
18164055 H.Schweikl, K.A.Hiller, A.Eckhardt, C.Bolay, G.Spagnuolo, T.Stempfl, and G.Schmalz (2008).
Differential gene expression involved in oxidative stress response caused by triethylene glycol dimethacrylate.
  Biomaterials, 29, 1377-1387.  
18298791 J.den Hertog, A.Ostman, and F.D.Böhmer (2008).
Protein tyrosine phosphatases: regulatory mechanisms.
  FEBS J, 275, 831-847.  
18423411 Y.M.Janssen-Heininger, B.T.Mossman, N.H.Heintz, H.J.Forman, B.Kalyanaraman, T.Finkel, J.S.Stamler, S.G.Rhee, and A.van der Vliet (2008).
Redox-based regulation of signal transduction: principles, pitfalls, and promises.
  Free Radic Biol Med, 45, 1.  
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.