PDBsum entry 3bm8

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Hydrolase PDB id
Protein chain
282 a.a. *
Waters ×73
* Residue conservation analysis
PDB id:
Name: Hydrolase
Title: Crystal structure of yoph mutant d356a complexed with irreversible inhibitor pvsn
Structure: Tyrosine-protein phosphatase yoph. Chain: a. Fragment: yoph catalytic domain. Synonym: virulence protein. Engineered: yes. Mutation: yes
Source: Yersinia enterocolitica. Gene: yoph, yop51. Expressed in: escherichia coli.
2.70Å     R-factor:   0.179     R-free:   0.278
Authors: Z.Y.Zhang,S.J.Liu
Key ref: S.Liu et al. (2008). Aryl vinyl sulfonates and sulfones as active site-directed and mechanism-based probes for protein tyrosine phosphatases. J Am Chem Soc, 130, 8251-8260. PubMed id: 18528979
12-Dec-07     Release date:   17-Jun-08    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P15273  (YOPH_YEREN) -  Tyrosine-protein phosphatase YopH
468 a.a.
282 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     dephosphorylation   2 terms 
  Biochemical function     phosphatase activity     2 terms  


J Am Chem Soc 130:8251-8260 (2008)
PubMed id: 18528979  
Aryl vinyl sulfonates and sulfones as active site-directed and mechanism-based probes for protein tyrosine phosphatases.
S.Liu, B.Zhou, H.Yang, Y.He, Z.X.Jiang, S.Kumar, L.Wu, Z.Y.Zhang.
Protein tyrosine phosphatases (PTPs) play key roles in the regulation of normal and pathological processes ranging from cell proliferation, differentiation, metabolism, and survival to many human diseases including cancer and diabetes. Functional studies of PTP can be greatly facilitated by small molecule probes that covalently label the active site of a PTP through an activity-dependent chemical reaction. In this article, we characterize phenyl vinyl sulfonate (PVSN) and phenyl vinyl sulfone (PVS) as a new class of mechanism-based PTP probes. PVSN and PVS inactivate a broad range of PTPs in a time- and concentration-dependent fashion. The PVSN- and PVS-mediated PTP inactivation is active site-directed and irreversible, resulting from a Michael addition of the active-site Cys Sgamma onto the terminal carbon of the vinyl group. Structural and mechanistic analyses reveal the molecular basis for the preference of PVSN/PVS toward the PTPs, which lies in the ability of PVSN and PVS to engage the conserved structural and catalytic machinery of the PTP active site. In contrast to early alpha-bromobenzyl phosphonate-based probes, PVSN and PVS are resistant to solvolysis and are cell-permeable and thus hold promise for in vivo applications. Collectively, these properties bode well for the development of aryl vinyl sulfonate/sulfone-based PTP probes to interrogate PTP activity in complex proteomes.

Literature references that cite this PDB file's key reference

  PubMed id Reference
  21365709 F.M.Koch, and R.Peters (2011).
Lewis acid/base catalyzed [2+2]-cycloaddition of sulfenes and aldehydes: a versatile entry to chiral sulfonyl and sulfinyl derivatives.
  Chemistry, 17, 3679-3692.  
21240419 L.Piovan, L.Wu, Z.Y.Zhang, and L.H.Andrade (2011).
Hypervalent organochalcogenanes as inhibitors of protein tyrosine phosphatases.
  Org Biomol Chem, 9, 1347-1351.  
20093358 C.Juliana, T.Fernandes-Alnemri, J.Wu, P.Datta, L.Solorzano, J.W.Yu, R.Meng, A.A.Quong, E.Latz, C.P.Scott, and E.S.Alnemri (2010).
Anti-inflammatory compounds parthenolide and Bay 11-7082 are direct inhibitors of the inflammasome.
  J Biol Chem, 285, 9792-9802.  
20062871 K.A.Kalesh, L.P.Tan, K.Lu, L.Gao, J.Wang, and S.Q.Yao (2010).
Peptide-based activity-based probes (ABPs) for target-specific profiling of protein tyrosine phosphatases (PTPs).
  Chem Commun (Camb), 46, 589-591.  
19716756 D.Krishnamurthy, and A.M.Barrios (2009).
Profiling protein tyrosine phosphatase activity with mechanistic probes.
  Curr Opin Chem Biol, 13, 375-381.  
19557267 M.Pitscheider, and S.A.Sieber (2009).
Cinnamic aldehyde derived probes for the active site labelling of pathogenesis associated enzymes.
  Chem Commun (Camb), (), 3741-3743.  
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.