- The representation displayed is that of cyclin-dependent kinase 2 (CDK2) interacting with an oxindole inhibitor. The ligand pictured is the , 4-(5-bromo-2-oxo-2h-indol-3-ylazo)- benzenesulfonamide. is part of the Ser/Thr protein kinases. CDK2 is a positive regulator of the eukaryotic cell cycle progression and is a catalytic unit that helps the cell progress from the G1 phase to the S phase. [1]
- In the study “The Structure of Cyclin-Dependent Kinase 2 (CDK2) in Complex with an Oxindole Inhibitor,” researchers studied whether using a topical oxindole inhibitor would reduce the chemotherapy-induced alopecia (CIA). Alopecia is characterized by hair loss. By inhibiting the CDK2, the cell cycle is slowed and the sensitivity to the epithelium from many cell cycle-active antitumor agents is reduced. Thus, a reduction in hair loss can be possible. [2]
- The oxindole inhibitor interacts with the CDK2 through a small .
- The CDK2 is composed of a total of 7 alpha-helices and 6 beta-sheets. The can be seen here.
- This presentation of the protein-ligand module shows the in which the oxindole inhibitor interacts with CDK2.
- The oxindole inhibitor interacts with in a Pi-Pi, Pi-cation interaction. An interaction between the oxindole inhibitor and can be seen here in a hydrophobic interaction. Also, there are two sets of important hydrogen bonds between the oxindole inhibitor and CDK2: and . It is with these four that the oxindole inhibitor is able to interact with CDK2 and slow the cell cycle.
References
- ↑ [1]
- ↑ Davis ST, Benson BG, Bramson HN, Chapman DE, Dickerson SH, Dold KM, Eberwein DJ, Edelstein M, Frye SV, Gampe Jr RT, Griffin RJ, Harris PA, Hassell AM, Holmes WD, Hunter RN, Knick VB, Lackey K, Lovejoy B, Luzzio MJ, Murray D, Parker P, Rocque WJ, Shewchuk L, Veal JM, Walker DH, Kuyper LF. Prevention of chemotherapy-induced alopecia in rats by CDK inhibitors. Science. 2001 Jan 5;291(5501):134-7. PMID:11141566 doi:10.1126/science.291.5501.134
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