The Rat Sarcoma (RAS) family (NRAS, HRAS, and KRAS) is endowed with GTPase activity to regulate various signaling pathways in ubiquitous animal cells. As proto-oncogenes, RAS mutations can maintain activation, leading to the growth and proliferation of abnormal cells and the development of a variety of human cancers. For the fight against tumors, the discovery of RAS-targeted drugs is of high significance. On the one hand, the structural properties of the RAS protein make it difficult to find inhibitors specifically targeted to it. On the other hand, targeting other molecules in the RAS signaling pathway often leads to severe tissue toxicities due to the lack of disease specificity. However, computer-aided drug design (CADD) can help solve the above problems. As an interdisciplinary approach that combines computational biology with medicinal chemistry, CADD has brought a variety of advances and numerous benefits to drug design, such as the rapid identification of new targets and discovery of new drugs. Based on an overview of RAS features and the history of inhibitor discovery, this review provides insight into the application of mainstream CADD methods to RAS drug design.
Anaphase Promoting Complex/Cyclosome (APC/C) is a kind of E3 ubiquitin ligase involved in a variety of biological processes including mitosis, senescence, apoptosis, and tumor cell formation. Its structural changes and major functions are closely related to the cell cycle progression. APC/C is a large complex consisting of multiple subunits, and the catalytic core exhibits the typical characteristics of the cullin-Ring E3 ligase. The function of the APC/C was modulated by the binding and separation of its co-activators and inhibitors and the corresponding conformational changes of APC/C itself. Ubiquitination is realized through the interaction with UBE2C and UBE2S E2 enzymes and substrates. Therefore, studying the structural changes of APC/C in the cell cycle species is helpful to understand the progression, the specific process of ubiquitination of E3 ubiquitin ligase, and how macromolecular components regulate activity through structural and conformational changes, which is conducive to the development of molecular biology, cell biology, pharmacology, oncology, and other fields. This paper will focus on APC/C’s molecular structure changes and biological functions in different processes of the cell cycle from the perspective of cell cycle progression.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.