Dipeptidyl Peptidase‐4 Is a Target Protein of Epigallocatechin‐3‐Gallate

Abstract

Epigallocatechin-3-gallate (EGCG), a major active ingredient in green tea, has various health benefits. It affects glucose metabolism, but the mechanism is not well understood. This study aimed to identify targets of EGCG related to glucose metabolism. The core fragment of EGCG is a flavonoid. The flavonoid scaffold was used as a substructure to find proteins cocrystallized with flavonoids in the Protein Data Bank. The proteins identified were screened in PubMed for known relationships with diabetes. Dipeptidyl peptidase-4 (DPP4; PDB 5J3J) was identified following this approach. By molecular docking, the interactions of EGCG and DPP4 were assessed. To test the stability of the interactions between EGCG and DPP4, molecular dynamics simulation for 100 ns was performed using Desmond software. In vitro, the concentration of EGCG required to inhibit DPP4 activity by 50% (the IC50 value) was 28.42 μM. These data provide a theoretical basis for intervention in glucose metabolism with EGCG.

Investigation of 1, 3, 4 Oxadiazole Derivative in PTZ-Induced Neurodegeneration: A Simulation and Molecular Approach

“…After molecular docking studies molecular dynamics simulations study of three complexes B3-GABA, DZM-GABA and FLZ-GABA were carried out using Desmond software package to tracked molecular interaction. 16 In MD simulation the complexes were immersed in an autocalculated orthorhombic box which was added with 68444, 68446 and 68441 for complexes B3-GABA, DZM-GABA and FLZ-GABA respectively using simple point charge water model. The optimization of the model is further done with optimized potential for liquid simulations (OPLS5).…”

“…The data presented as is complying with the previously published data. 16,17 Effect of B3 on PTZ-Induced Seizures Administration of intraperitoneal (i.p) injection of B3 at 20 and 40 mg/kg resulted in the protection of 50.0% and 83.33% of animal respectively in PTZ-induced mortality.…”

“…The obtained results of docking and MD simulation were in line with the already published data and hence we perform animal studies. [15][16][17] In animal studies various types of…”

Distal mutation V486M disrupts the catalytic activity of DPP4 by affecting the flap of the propeller domain

“…Recently, Maxwell et al revealed over 50 cryptic epitopes by 0.1 s simulations of the SARS-CoV-2 proteome [ 22 ]. To date, MD simulations of DPP4 have been used for virtual screening and exploring the binding mechanism of inhibitors [ 23 , 24 ]. As summarized in several reviews [ 13 – 16 ], major improvements in MD sampling efficiency have expanded the impact of biomolecular simulations in drug discovery and design, which has increased the appeal of theoretical simulations for researches.…”

Partial Purification of Dipeptidyl Peptidase-4 From Human Blood Serum and Study the Inhibitory Effect of Some Nitrile Derivatives on it

“…Dipeptidyl peptidase-4 also has nonglycemic effects by controlling the progression of inflammation, which may be mediated more through direct protein-protein interactions than catalytic activity in the context of nonalcoholic fatty liver disease, obesity and type 2 diabetes T2DM [4] . The Dpp-4 enzyme is present in many human tissues, including the pancreas,fat cells,liver,and as proteases present on the cell surface [5] . Some studies have reported associations of Dpp-4 with infection or attenuation of lung injury [6,7] Others have discovered numerous Dpp4 transcripts in the nasal epithelia of children and revealed the up-regulation of CD26 on human T lymphocytes upon a correlation with soluble Dpp4 activity [8] .…”