RESEARCH: CANCER
FOLDING PROJECT #16493 PROFILE

This project studies RIPK2, a protein involved in cancer growth. Researchers are using computer models to see how 3 known inhibitors block RIPK2 from interacting with another protein called XIAP. This could help develop better cancer drugs.

Kinases are a major target for a variety of cancer therapies, but their mechanism of action is relatively unknown at a detailed atomic level, preventing us from understanding and optimizing known inhibitors.

One example is the Serine/Threonine Kinase RIPK2.

RIPK2 inhibition is useful for cancer targeting as it prevents RIPK2 from binding a protein partner named XIAP.

In fact, there are already 3 known inhibitors that bind to RIPK2 and prevent RIPK2-XIAP binding! However, it remains difficult to optimize these ligands for clinical purposes because we do not understand how any of these three inhibitors actually act on RIPK2 to prevent XIAP binding behavior.

These four projects are simulating RIPK2 by itself and bound to each of the three inhibitors, with the hope that this will reveal a more detailed mechanism of how each inhibitor works to prevent XIAP binding.

As a bonus, this will help reveal how RIPK2 *binds* XIAP (also unknown)! In this set of projects we are studying the following systems: 16466 – RIPK2 16467 – RIPK2:CSLP43 inhibitor-bound complex 16468 – RIPK2:CSLP48 inhibitor-bound complex 16469 – RIPK2:GSK583 inhibitor-bound complex 16470 – RIPK2:WEHI-345 inhibitor-bound complex 16471 – RIPK2:BI inhibitor-bound complex 16488 – RIPK2:BI inhibitor-bound complex (alt configuration) 16489 – RIPK2:BI inhibitor-bound complex (alt configuration 2) 16490 – RIPK2:NVS inhibitor-bound complex 16491 – RIPK2 apo from the GSK bound structure 16492 – RIPK2 apo fro the BI bound structure 16493 – RIPK2 apo from a Gefitinib bound structure 16494 – RIPK2 apo from a Novartis-produced inhibitor 16495 – RIPK2:Gefitinib complex 16496 – RIPK2:Novartis inhibitor structure.

Kinases

Enzymes that transfer phosphate groups to molecules.

Kinases are a crucial type of enzyme involved in many cellular processes. They add phosphate groups to other molecules, acting like switches to turn processes on or off. This makes them important targets for cancer therapies because cancer cells often have abnormal kinase activity.

RIPK2

Receptor-interacting protein kinase 2

RIPK2 is a protein that plays a role in the body's immune response. It's involved in signaling pathways triggered by infections or cellular damage. Researchers are studying RIPK2 as a potential target for treating inflammatory diseases and cancer because its overactivity can contribute to these conditions.

XIAP

X-linked inhibitor of apoptosis protein

XIAP is a protein that blocks programmed cell death (apoptosis). Cancer cells often overexpress XIAP to evade destruction. Inhibiting XIAP could be a strategy for killing cancer cells.

Inhibitors

Substances that block the activity of a target molecule.

Inhibitors are molecules designed to prevent or reduce the action of other molecules. They are crucial tools in drug development because they can be used to target specific proteins involved in disease processes.

Ligands

Molecules that bind to receptors or other target proteins.

Ligands are molecules that have a specific shape and chemical properties allowing them to bind to target molecules like proteins. They play important roles in biological processes and are often used in drug development as they can be designed to activate or inhibit specific targets.

Apoptosis

Programmed cell death.

Apoptosis is a natural process of cell death that's essential for development and maintaining healthy tissues. It involves a series of carefully controlled steps that lead to the dismantling and removal of cells. Dysregulation of apoptosis can contribute to diseases like cancer.