Protein kinase C βII in diabetic complications: survey of structural, biological and computational studies

Area of Science:

• Biochemistry
• Pharmacology
• Computational Biology

Background:

• Protein kinase C beta-II (PKC-βII) is overexpressed in hyperglycemia, contributing to diabetic complications like cardiovascular issues, nephropathy, neuropathy, and retinopathy.
• Selective inhibition of PKC-βII is a promising therapeutic strategy for diabetes-related complications.
• Achieving isoform-selective inhibition of PKC-βII is challenging due to high sequence homology with other PKC isoforms.

Purpose of the Study:

• To review current research on PKC-βII, focusing on its biological roles and structural characteristics.
• To summarize structure-activity relationship (SAR) studies and in silico approaches for designing PKC-βII inhibitors.
• To evaluate the potential of PKC-βII as a therapeutic target and the role of computational methods in inhibitor development.

Main Methods:

• Review of existing literature on PKC-βII.
• Summary of biological and crystal structure data.
• Inclusion of in silico studies: homology modeling, molecular docking, molecular dynamics, QSAR, and pharmacophore modeling.

Main Results:

• PKC-βII is implicated in various diabetic complications.
• Structure-activity relationship studies provide insights into inhibitor design.
• In silico tools have been applied to understand PKC-βII structure and interactions.

Conclusions:

• PKC-βII remains a significant target for managing diabetes-related complications.
• Selective inhibitors are in clinical trials, but success is not yet achieved.
• In silico approaches are valuable for designing and optimizing selective PKC-βII inhibitors.