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PDBsum entry 3h2x

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protein ligands links
Hydrolase PDB id
3h2x
Jmol
Contents
Protein chain
302 a.a. *
Ligands
PO4 ×5
Waters ×201
* Residue conservation analysis
PDB id:
3h2x
Name: Hydrolase
Title: Crystal structure of the human lymphoid tyrosine phosphatase catalytic domain
Structure: Tyrosine-protein phosphatase non-receptor type 22. Chain: a. Fragment: catalytic domain. Synonym: hematopoietic cell protein-tyrosine phosphatase 70z-pep, lymphoid phosphatase, lyp. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: ptpn22, ptpn8. Expressed in: escherichia coli. Expression_system_taxid: 562.
Resolution:
2.20Å     R-factor:   0.176     R-free:   0.204
Authors: S.J.Tsai,U.Sen
Key ref: S.J.Tsai et al. (2009). Crystal structure of the human lymphoid tyrosine phosphatase catalytic domain: insights into redox regulation . Biochemistry, 48, 4838-4845. PubMed id: 19371084
Date:
14-Apr-09     Release date:   02-Jun-09    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
Q9Y2R2  (PTN22_HUMAN) -  Tyrosine-protein phosphatase non-receptor type 22
Seq:
Struc:
 
Seq:
Struc:
807 a.a.
302 a.a.
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: 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
Bound ligand (Het Group name = PO4)
corresponds exactly
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  

 

 
    reference    
 
 
Biochemistry 48:4838-4845 (2009)
PubMed id: 19371084  
 
 
Crystal structure of the human lymphoid tyrosine phosphatase catalytic domain: insights into redox regulation .
S.J.Tsai, U.Sen, L.Zhao, W.B.Greenleaf, J.Dasgupta, E.Fiorillo, V.Orrú, N.Bottini, X.S.Chen.
 
  ABSTRACT  
 
The lymphoid tyrosine phosphatase (LYP), encoded by the PTPN22 gene, recently emerged as an important risk factor and drug target for human autoimmunity. Here we solved the structure of the catalytic domain of LYP, which revealed noticeable differences with previously published structures. The active center with a semi-closed conformation binds a phosphate ion, which may represent an intermediate conformation after dephosphorylation of the substrate but before release of the phosphate product. The structure also revealed an unusual disulfide bond formed between the catalytic Cys and one of the two Cys residues nearby, which is not observed in previously determined structures. Our structural and mutagenesis data suggest that the disulfide bond may play a role in protecting the enzyme from irreversible oxidation. Surprisingly, we found that the two noncatalytic Cys around the active center exert an opposite yin-yang regulation on the catalytic Cys activity. These detailed structural and functional characterizations have provided new insights into autoregulatory mechanisms of LYP function.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
20083307 M.R.Karver, D.Krishnamurthy, N.Bottini, and A.M.Barrios (2010).
Gold(I) phosphine mediated selective inhibition of lymphoid tyrosine phosphatase.
  J Inorg Biochem, 104, 268-273.  
20204370 S.M.Stanford, T.M.Mustelin, and N.Bottini (2010).
Lymphoid tyrosine phosphatase and autoimmunity: human genetics rediscovers tyrosine phosphatases.
  Semin Immunopathol, 32, 127-136.  
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.  
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.