PDBsum entry 5bug

Hydrolase

PDB id: 5bug

Contents

Protein chains

314 a.a.

Ligands

TLA ×4

Waters ×751

PDB id:

5bug

Name:

Hydrolase

Title:

Crystal structure of human phosphatase pten oxidized by h2o2

Structure:

Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase pten. Chain: a, b, c, d. Fragment: pten wt 14-351 delta 286-309. Synonym: mutated in multiple advanced cancers 1,phosphatase and tensin homolog. Engineered: yes. Mutation: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: pten, mmac1, tep1. Expressed in: trichoplusia ni. Expression_system_taxid: 7111.

Resolution:

2.40Å R-factor: 0.177 R-free: 0.211

Authors:

C.-U.Lee,D.Bier,S.Hennig,T.N.Grossmann

Key ref:

C.U.Lee et al. (2015). Redox Modulation of PTEN Phosphatase Activity by Hydrogen Peroxide and Bisperoxidovanadium Complexes. Angew Chem Int Ed Engl, 54, 13796-13800. PubMed id: 26418532 DOI: 10.1002/anie.201506338

Date:

03-Jun-15 Release date: 07-Oct-15

Protein chains

P60484  (PTEN_HUMAN) -  Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN from Homo sapiens

Seq: 403 a.a.

Struc: 314 a.a.

Enzyme reactions

• Enzyme class 1: E.C.3.1.3.- - ?????
• Enzyme class 2: E.C.3.1.3.16 - protein-serine/threonine phosphatase.
• Reaction:
  1. O-phospho-L-seryl-[protein] + H2O = L-seryl-[protein] + phosphate
  2. O-phospho-L-threonyl-[protein] + H2O = L-threonyl-[protein] + phosphate
• Enzyme class 3: E.C.3.1.3.48 - protein-tyrosine-phosphatase.
• Reaction: O-phospho-L-tyrosyl-[protein] + H2O = L-tyrosyl-[protein] + phosphate
• Enzyme class 4: E.C.3.1.3.67 - phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase.

Pathway:

• Reaction: a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-3,4,5-trisphosphate) + H2O = a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-4,5- bisphosphate) + phosphate
• Cofactor: Mg(2+)

Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

DOI no: 10.1002/anie.201506338

Angew Chem Int Ed Engl 54:13796-13800 (2015)

PubMed id: 26418532

Redox Modulation of PTEN Phosphatase Activity by Hydrogen Peroxide and Bisperoxidovanadium Complexes.

C.U.Lee, G.Hahne, J.Hanske, T.Bange, D.Bier, C.Rademacher, S.Hennig, T.N.Grossmann.

ABSTRACT

PTEN is a dual-specificity protein tyrosine phosphatase. As one of the central tumor suppressors, a thorough regulation of its activity is essential for proper cellular homeostasis. The precise implications of PTEN inhibition by reactive oxygen species (e.g. H2 O2 ) and the subsequent structural consequences remain elusive. To study the effects of PTEN inhibition, bisperoxidovanadium (bpV) complexes serve as important tools with the potential for the treatment of nerve injury or cardiac ischemia. However, their mode of action is unknown, hampering further optimization and preventing therapeutic applications. Based on protein crystallography, mass spectrometry, and NMR spectroscopy, we elucidate the molecular basis of PTEN inhibition by H2 O2 and bpV complexes. We show that both molecules inhibit PTEN via oxidative mechanisms resulting in the formation of the same intramolecular disulfide, therefore enabling the reactivation of PTEN under reductive conditions.