Human Protein Tyrosine Phosphatase 1B (PTP1B): From Structure to Clinical Inhibitor Perspectives

Phosphorylation is an essential process in biological events and is considered critical for biological functions. In tissues, protein phosphorylation mainly occurs on tyrosine (Tyr), serine (Ser) and threonine (Thr) residues. The balance between phosphorylation and dephosphorylation is under the con...

Full description

Saved in:
Bibliographic Details
Published in:International journal of molecular sciences 2022-06, Vol.23 (13), p.7027
Main Authors: Liu, Rongxing, Mathieu, Cécile, Berthelet, Jérémy, Zhang, Wenchao, Dupret, Jean-Marie, Rodrigues Lima, Fernando
Format: Article
Language:English
Subjects:
Allosteric properties
Binding sites
Biological activity
Cell cycle
challenge
Clinical trials
crystal structure
Dephosphorylation
Diabetes
Diabetes mellitus
Drug delivery
Drugs
Enzymes
Growth factors
inhibitors
Insulin
Kinases
Life Sciences
Metabolism
mRNA
Phosphatase
Phosphorylation
Physiology
Protein kinase
Protein-tyrosine-phosphatase
Proteins
PTP1B
Regulation
Reviews
Signal transduction
specificity
Tyrosine
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Phosphorylation is an essential process in biological events and is considered critical for biological functions. In tissues, protein phosphorylation mainly occurs on tyrosine (Tyr), serine (Ser) and threonine (Thr) residues. The balance between phosphorylation and dephosphorylation is under the control of two super enzyme families, protein kinases (PKs) and protein phosphatases (PPs), respectively. Although there are many selective and effective drugs targeting phosphokinases, developing drugs targeting phosphatases is challenging. PTP1B, one of the most central protein tyrosine phosphatases (PTPs), is a key player in several human diseases and disorders, such as diabetes, obesity, and hematopoietic malignancies, through modulation of different signaling pathways. However, due to high conservation among PTPs, most PTP1B inhibitors lack specificity, raising the need to develop new strategies targeting this enzyme. In this mini-review, we summarize three classes of PTP1B inhibitors with different mechanisms: (1) targeting multiple aryl-phosphorylation sites including the catalytic site of PTP1B; (2) targeting allosteric sites of PTP1B; (3) targeting specific mRNA sequence of PTP1B. All three types of PTP1B inhibitors present good specificity over other PTPs and are promising for the development of efficient small molecules targeting this enzyme.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms23137027