Cyclin B1 RxL substrate-binding groove (CCNB1 RxL groove)

The Cyclin B1 RxL substrate-binding groove, often referred to as the hydrophobic patch, is a specialized structural domain on the surface of Cyclin B1 that facilitates the recruitment of specific substrates to the Cyclin B1-CDK1 kinase complex. This groove recognizes and binds to a conserved 'RxL' (Arg-x-Leu) motif, also known as the Cy-motif, found in many cell cycle regulatory proteins such as p21, p27, and various mitotic substrates. By mediating these protein-protein interactions, the RxL groove ensures the efficient and timely phosphorylation of key targets required for the G2/M transition and proper mitotic progression. In many cancers, Cyclin B1 is overexpressed, leading to uncontrolled cell proliferation and genomic instability, making this binding groove an attractive target for therapeutic intervention. Small molecules or peptides designed to block this groove can selectively inhibit the recruitment of mitotic substrates without directly targeting the ATP-binding site of CDK1, potentially offering a more specific mechanism for arresting the cell cycle in malignant cells.

Other names

Cyclin B1 hydrophobic patchCy-motif binding siteM-phase promoting factor substrate-binding siteCyclin B1 recruitment site

Competitive inhibition of substrate binding to the Cyclin B1-CDK1 complex by occupying the hydrophobic RxL-binding groove, thereby preventing the phosphorylation of specific mitotic substrates.