2J17

pTyr bound form of SDP-1

Summary for 2J17

• Entry DOI: 10.2210/pdb2j17/pdb
• Related: 2J16
• Descriptor: TYROSINE-PROTEIN PHOSPHATASE YIL113W, MAGNESIUM ION, O-PHOSPHOTYROSINE, ... (4 entities in total)
• Functional Keywords: hydrolase, protein phosphatase, hypothetical protein
• Biological source: SACCHAROMYCES CEREVISIAE (BAKER'S YEAST)
• Total number of polymer chains: 2
• Total formula weight: 42351.74

Authors

Briggs, D.C.,McDonald, N.Q. (deposition date: 2006-08-09, release date: 2007-05-22, Last modification date: 2024-11-06)

Primary citation

Fox, G.C.,Shafiq, M.,Briggs, D.C.,Knowles, P.P.,Collister, M.,Didmon, M.J.,Makrantoni, V.,Dickinson, R.J.,Hanrahan, S.,Totty, N.,Stark, M.J.,Keyse, S.M.,McDonald, N.Q.
Redox-mediated substrate recognition by Sdp1 defines a new group of tyrosine phosphatases.
Nature, 447:487-492, 2007

PubMed 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.

PubMed: 17495930
DOI: 10.1038/nature05804

Experimental method

X-RAY DIFFRACTION (2.84 Å)