Structural flexibility and interactions of PTP1B's S-loop

Interdisciplinary Sciences, Computational Life Sciences
Jing-Fang WangYixue Li

Abstract

Protein-tyrosine phosphatase 1B (PTP1B) is an attractive drug target for type II diabetes and obesity. The structural motions of its S-loop play crucial roles in WPD-loop closure that is essential for the catalytic mechanism of this protein. In the current studies, totally 20 ns molecular dynamics simulations were employed on both PTP1B and its complex with inhibitors in the explicit solution surroundings with the periodic boundary conditions in order to perform detail exam on the structural flexibility of S-loop. Together with calculating RMSD values and monitoring the distances between active site and the residues in S-loop, it is found that S-loop can move towards to active site and form a tight binding pocket for substrates upon inhibitor binding. And a hydrogen bond network rearrangement was detected in this region, which may cause the transforms of both the tree-dimensional structure and the total accessible surfaces for the residues in S loop. Additionally, the second structures of Ser201 and Gly209 have huge changes for the open system, which is not detected in close system. These findings can reveal the possible mechanism of ligand recognitions and inhibitions, further providing useful information to design novel inhib...Continue Reading

References

Mar 11, 1994·Science·D BarfordN K Tonks
Dec 11, 1999·Nucleic Acids Research·H M BermanP E Bourne
Jan 4, 2001·Physical Review. E, Statistical Physics, Plasmas, Fluids, and Related Interdisciplinary Topics·B Hess
Jun 20, 2001·FEBS Letters·K Kolmodin, J Aqvist
Aug 10, 2002·Proceedings of the National Academy of Sciences of the United States of America·Bradley A ZinkerMichael R Jirousek
Sep 5, 2002·Nature Reviews. Drug Discovery·Theodore O JohnsonMichael R Jirousek
Mar 11, 2003·American Journal of Physiology. Endocrinology and Metabolism·Ernest Asante-Appiah, Brian P Kennedy
Jul 20, 2004·Nature Structural & Molecular Biology·Christian WiesmannStig K Hansen
Aug 31, 2004·Acta Crystallographica. Section D, Biological Crystallography·Anja K PedersenJette S Kastrup
Feb 20, 2007·Biochemical and Biophysical Research Communications·Jing-Fang WangKuo-Chen Chou
Jan 29, 2008·Protein and Peptide Letters·Jing-Fang WangKuo-Chen Chou

❮ Previous
Next ❯

Citations

Jul 4, 2012·Journal of Chemical Information and Modeling·Sarath Kumar BaskaranBaddireddi Subhadra Lakshmi

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.