3ZV2: Human Protein-Tyrosine Phosphatase 1b C215a, S216a Mutant

Citation:
Abstract
Protein tyrosine phosphatase 1B (PTP1B) plays important roles in downregulation of insulin and leptin signaling and is an established therapeutic target for diabetes and obesity. PTP1B is regulated by reactive oxygen species (ROS) produced in response to various stimuli, including insulin. The reversibly oxidized form of the enzyme (PTP1B-OX) is inactive and undergoes profound conformational changes at the active site. We generated conformation-sensor antibodies, in the form of single-chain variable fragments (scFvs), that stabilize PTP1B-OX and thereby inhibit its phosphatase function. Expression of conformation-sensor scFvs as intracellular antibodies (intrabodies) enhanced insulin-induced tyrosyl phosphorylation of the beta subunit of the insulin receptor and its substrate IRS-1 and increased insulin-induced phosphorylation of PKB/AKT. Our data suggest that stabilization of the oxidized, inactive form of PTP1B with appropriate therapeutic molecules may offer a paradigm for phosphatase drug development.
PDB ID: 3ZV2Download
MMDB ID: 93396
PDB Deposition Date: 2011/7/22
Updated in MMDB: 2011/10
Experimental Method:
x-ray diffraction
Resolution: 2.8  Å
Source Organism:
Similar Structures:
Biological Unit for 3ZV2: monomeric; determined by author and by software (PISA)
Molecular Components in 3ZV2
Label Count Molecule
Protein (1 molecule)
1
Tyrosine-protein Phosphatase Non-receptor Type 1(Gene symbol: PTPN1)
Molecule annotation
* Click molecule labels to explore molecular sequence information.

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