PDBsum entry 1yts

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Hydrolase PDB id
Jmol PyMol
Protein chain
278 a.a. *
SO4 ×2
Waters ×60
* Residue conservation analysis
PDB id:
Name: Hydrolase
Title: A ligand-induced conformational change in the yersinia protein tyrosine phosphatase
Structure: Yersinia protein tyrosine phosphatase. Chain: a. Engineered: yes. Mutation: yes
Source: Yersinia enterocolitica. Organism_taxid: 630. Strain: w22703. Gene: yop51. Expressed in: escherichia coli. Expression_system_taxid: 562.
2.50Å     R-factor:   0.174    
Authors: H.L.Schubert,J.A.Stuckey,E.B.Fauman,J.E.Dixon,M.A.Saper
Key ref:
H.L.Schubert et al. (1995). A ligand-induced conformational change in the Yersinia protein tyrosine phosphatase. Protein Sci, 4, 1904-1913. PubMed id: 8528087 DOI: 10.1002/pro.5560040924
07-Apr-95     Release date:   10-Jul-95    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P15273  (YOPH_YEREN) -  Tyrosine-protein phosphatase YopH
468 a.a.
278 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 2 residue positions (black crosses)

 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     protein dephosphorylation   1 term 
  Biochemical function     protein tyrosine phosphatase activity     1 term  


DOI no: 10.1002/pro.5560040924 Protein Sci 4:1904-1913 (1995)
PubMed id: 8528087  
A ligand-induced conformational change in the Yersinia protein tyrosine phosphatase.
H.L.Schubert, E.B.Fauman, J.A.Stuckey, J.E.Dixon, M.A.Saper.
Protein tyrosine phosphatases (PTPases) play critical roles in the intracellular signal transduction pathways that regulate cell transformation, growth, and proliferation. The structures of several different PTPases have revealed a conserved active site architecture in which a phosphate-binding loop, together with an invariant arginine, cradle the phosphate of a phosphotyrosine substrate and poise it for nucleophilic attack by an invariant cysteine nucleophile. We previously reported that binding of tungstate to the Yop51 PTPase from Yersinia induced a loop conformational change that moved aspartic acid 356 into the active site, where it can function as a general acid. This is consistent with the aspartic acid donating a proton to the tyrosyl leaving group during the initial hydrolysis step. In this report, using a similar structure of the inactive Cys 403-->Ser mutant of the Yersinia PTPase complexed with sulfate, we detail the structural and functional details of this conformational change. In response to oxyanion binding, small perturbations occur in active site residues, especially Arg 409, and trigger the loop to close. Interestingly, the peptide bond following Asp 356 has flipped to ligate a buried, active site water molecule that also hydrogen bonds to the bound sulfate anion and two invariant glutamines. Loop closure also significantly decreases the solvent accessibility of the bound oxyanion and could effectively shield catalytic intermediates from phosphate acceptors other than water. We speculate that the intrinsic loop flexibility of different PTPases may be related to their catalytic rate and may play a role in the wide range of activities observed within this enzyme family.
  Selected figure(s)  
Figure 5.
Fig. 5. Conformationalchange in tpe WpDloopmoves Asp 356 into active site and3.6 A romnoxgen of the boundsulfate.The unbound structure (residues 354- 358) is shown in lueand the sulfate-bound structure is shown in yellow with red oxygens and blue nitrogens. The peptide ond between Asp 356 andGln 357 lips between thetwo formingatype 11 fi-turn in theclosed conformation with Gln 57 at the i + 2 position.Thefol- lowing is a list of , shifts between the two forms: Trp 354, 1.9 A; Pro 355,3.8 ; Asp356, 5.0 A; Gln 357, 6.7 A; Thr 358,4.4 A.
Figure 7.
Fig. 7. A watermoleculetrapped in theac- tive site f the sulfate-bound structure bridgestheclosedWpD loop andthebound oxyanion.The ater moleculeiswithin 3.3A of severalresiduesincludingthe .sulfate. istances from the waterare: 3.0 A to sul- ateoxygen 04 thatis nalogous to thescis- ileesterlinkage of phosphotyrosine,2.7 A o sylfateoxygen 02,3.2 A Gln 446 OE 1, .3 A o Gln450 Ne2, and 3.0br. to theam- de of Gln 357 on pD loop. The car- oxylsidechain of.Asp 356 A from he ater and .6 A from 04.
  The above figures are reprinted from an Open Access publication published by the Protein Society: Protein Sci (1995, 4, 1904-1913) copyright 1995.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20848551 A.Ahmed, S.Villinger, and H.Gohlke (2010).
Large-scale comparison of protein essential dynamics from molecular dynamics simulations and coarse-grained normal mode analyses.
  Proteins, 78, 3341-3352.  
19011046 Q.Pu, Y.Chang, C.Zhang, Y.Cai, and A.Hassid (2009).
Chronic insulin treatment suppresses PTP1B function, induces increased PDGF signaling, and amplifies neointima formation in the balloon-injured rat artery.
  Am J Physiol Heart Circ Physiol, 296, H132-H139.  
19140798 T.A.Brandão, H.Robinson, S.J.Johnson, and A.C.Hengge (2009).
Impaired acid catalysis by mutation of a protein loop hinge residue in a YopH mutant revealed by crystal structures.
  J Am Chem Soc, 131, 778-786.
PDB codes: 3f99 3f9a 3f9b
18084305 L.Chen, H.Wang, J.Zhang, L.Gu, N.Huang, J.M.Zhou, and J.Chai (2008).
Structural basis for the catalytic mechanism of phosphothreonine lyase.
  Nat Struct Mol Biol, 15, 101-102.
PDB codes: 2z8m 2z8n 2z8o 2z8p
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.  
19012396 S.Liu, L.F.Zeng, L.Wu, X.Yu, T.Xue, A.M.Gunawan, Y.Q.Long, and Z.Y.Zhang (2008).
Targeting inactive enzyme conformation: aryl diketoacid derivatives as a new class of PTP1B inhibitors.
  J Am Chem Soc, 130, 17075-17084.
PDB codes: 3eax 3eb1
17154432 A.K.Hirsch, F.R.Fischer, and F.Diederich (2007).
Phosphate recognition in structural biology.
  Angew Chem Int Ed Engl, 46, 338-352.  
17766352 Z.Huang, and C.F.Wong (2007).
A mining minima approach to exploring the docking pathways of p-nitrocatechol sulfate to YopH.
  Biophys J, 93, 4141-4150.  
16607668 G.Roos, S.Loverix, E.Brosens, K.Van Belle, L.Wyns, P.Geerlings, and J.Messens (2006).
The activation of electrophile, nucleophile and leaving group during the reaction catalysed by pI258 arsenate reductase.
  Chembiochem, 7, 981-989.  
16698773 X.Hu, and C.E.Stebbins (2006).
Dynamics of the WPD loop of the Yersinia protein tyrosine phosphatase.
  Biophys J, 91, 948-956.  
15008850 J.M.Otaki, and H.Yamamoto (2004).
Species-specific color-pattern modifications of butterfly wings.
  Dev Growth Differ, 46, 1.  
15459456 J.M.Otaki, and H.Yamamoto (2004).
Color-pattern modifications and speciation in butterflies of the genus Vanessa and its related genera Cynthia and Bassaris.
  Zoolog Sci, 21, 967-976.  
11980490 H.Deng, R.Callender, Z.Huang, and Z.Y.Zhang (2002).
Is the PTPase-vanadate complex a true transition state analogue?
  Biochemistry, 41, 5865-5872.  
12072565 J.Messens, J.C.Martins, K.Van Belle, E.Brosens, A.Desmyter, M.De Gieter, J.M.Wieruszeski, R.Willem, L.Wyns, and I.Zegers (2002).
All intermediates of the arsenate reductase mechanism, including an intramolecular dynamic disulfide cascade.
  Proc Natl Acad Sci U S A, 99, 8506-8511.
PDB codes: 1ljl 1lju 1lk0
11863439 M.A.Schumacher, J.L.Todd, A.E.Rice, K.G.Tanner, and J.M.Denu (2002).
Structural basis for the recognition of a bisphosphorylated MAP kinase peptide by human VHR protein Phosphatase.
  Biochemistry, 41, 3009-3017.
PDB code: 1j4x
11468356 G.Scapin, S.Patel, V.Patel, B.Kennedy, and E.Asante-Appiah (2001).
The structure of apo protein-tyrosine phosphatase 1B C215S mutant: more than just an S --> O change.
  Protein Sci, 10, 1596-1605.
PDB code: 1i57
11585896 J.N.Andersen, O.H.Mortensen, G.H.Peters, P.G.Drake, L.F.Iversen, O.H.Olsen, P.G.Jansen, H.S.Andersen, N.K.Tonks, and N.P.Møller (2001).
Structural and evolutionary relationships among protein tyrosine phosphatase domains.
  Mol Cell Biol, 21, 7117-7136.  
10777720 G.H.Peters, T.M.Frimurer, J.N.Andersen, and O.H.Olsen (2000).
Molecular dynamics simulations of protein-tyrosine phosphatase 1B. II. substrate-enzyme interactions and dynamics.
  Biophys J, 78, 2191-2200.  
10692338 G.Zhou, W.R.Ellington, and M.S.Chapman (2000).
Induced fit in arginine kinase.
  Biophys J, 78, 1541-1550.  
11056007 J.C.Li, E.T.Samy, J.Grima, S.S.Chung, D.Mruk, W.M.Lee, B.Silvestrini, and C.Y.Cheng (2000).
Rat testicular myotubularin, a protein tyrosine phosphatase expressed by Sertoli and germ cells, is a potential marker for studying cell-cell interactions in the rat testis.
  J Cell Physiol, 185, 366-385.  
10735562 N.R.Glover, and A.S.Tracey (2000).
The phosphatase domains of LAR, CD45, and PTP1B: structural correlations with peptide-based inhibitors.
  Biochem Cell Biol, 78, 39-50.  
10625478 R.H.Hoff, A.C.Hengge, L.Wu, Y.F.Keng, and Z.Y.Zhang (2000).
Effects on general acid catalysis from mutations of the invariant tryptophan and arginine residues in the protein tyrosine phosphatase from Yersinia.
  Biochemistry, 39, 46-54.  
10978163 W.Chen, M.Wilborn, and J.Rudolph (2000).
Dual-specific Cdc25B phosphatase: in search of the catalytic acid.
  Biochemistry, 39, 10781-10789.  
10625489 Z.Q.Wen, and G.J.Thomas (2000).
Ultraviolet-resonance raman spectroscopy of the filamentous virus Pf3: interactions of Trp 38 specific to the assembled virion subunit.
  Biochemistry, 39, 146-152.  
10092868 Y.F.Keng, L.Wu, and Z.Y.Zhang (1999).
Probing the function of the conserved tryptophan in the flexible loop of the Yersinia protein-tyrosine phosphatase.
  Eur J Biochem, 259, 809-814.  
9763224 B.L.Martin (1998).
Inhibition of calcineurin by the tyrphostin class of tyrosine kinase inhibitors.
  Biochem Pharmacol, 56, 483-488.  
9799489 F.Wang, W.Li, M.R.Emmett, C.L.Hendrickson, A.G.Marshall, Y.L.Zhang, L.Wu, and Z.Y.Zhang (1998).
Conformational and dynamic changes of Yersinia protein tyrosine phosphatase induced by ligand binding and active site mutation and revealed by H/D exchange and electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry.
  Biochemistry, 37, 15289-15299.  
9548920 G.H.Peters, T.M.Frimurer, and O.H.Olsen (1998).
Electrostatic evaluation of the signature motif (H/V)CX5R(S/T) in protein-tyrosine phosphatases.
  Biochemistry, 37, 5383-5393.  
9818190 J.M.Denu, and J.E.Dixon (1998).
Protein tyrosine phosphatases: mechanisms of catalysis and regulation.
  Curr Opin Chem Biol, 2, 633-641.  
9757831 M.J.Wishart, and J.E.Dixon (1998).
Gathering STYX: phosphatase-like form predicts functions for unique protein-interaction domains.
  Trends Biochem Sci, 23, 301-306.  
9922143 M.R.Groves, Z.J.Yao, P.P.Roller, T.R.Burke, and D.Barford (1998).
Structural basis for inhibition of the protein tyrosine phosphatase 1B by phosphotyrosine peptide mimetics.
  Biochemistry, 37, 17773-17783.
PDB codes: 1bzc 1bzh 1bzj
9817026 T.R.Burke, and Z.Y.Zhang (1998).
Protein-tyrosine phosphatases: structure, mechanism, and inhibitor discovery.
  Biopolymers, 47, 225-241.  
9047324 L.J.Juszczak, Z.Y.Zhang, L.Wu, D.S.Gottfried, and D.D.Eads (1997).
Rapid loop dynamics of Yersinia protein tyrosine phosphatases.
  Biochemistry, 36, 2227-2236.  
9063884 Z.Y.Zhang, and L.Wu (1997).
The single sulfur to oxygen substitution in the active site nucleophile of the Yersinia protein-tyrosine phosphatase leads to substantial structural and functional perturbations.
  Biochemistry, 36, 1362-1369.  
8679534 A.C.Hengge, J.M.Denu, and J.E.Dixon (1996).
Transition-state structures for the native dual-specific phosphatase VHR and D92N and S131A mutants. Contributions to the driving force for catalysis.
  Biochemistry, 35, 7084-7092.  
8987394 E.B.Fauman, and M.A.Saper (1996).
Structure and function of the protein tyrosine phosphatases.
  Trends Biochem Sci, 21, 413-417.  
  8771191 J.W.Eckstein, P.Beer-Romero, and I.Berdo (1996).
Identification of an essential acidic residue in Cdc25 protein phosphatase and a general three-dimensional model for a core region in protein phosphatases.
  Protein Sci, 5, 5.  
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 codes are shown on the right.