RESEARCH: CANCER
FOLDING PROJECT #12475 PROFILE

Pin1 is a protein that helps cells send signals. It works by changing shape when it binds to specific molecules. This project uses computer simulations to understand how Pin1 changes shape and activates, which could lead to new cancer treatments.

Note: This TLDR is a simplication and may not be 100% accurate.

Human Pin1 is a peptidyl prolyl isomerase (PPI) involved in many cell signaling processes and a target for cancer therapeutics.

The job of this protein is to recognize proline residues next to phosphorylated serines and threonines, and catalyze the cis/trans isomerization of the proline backbone. Pin1 has two domains that both recognize these motifs: a catalytic domain, and a so-called WW domain, which exists in a conformational equilibrium between and a compact and extended state.

When peptide substrates are present, there is a shift in the conformational equilibrium between compact and extended states, which is in turn coupled to allosteric changes in the catalytic domain that activates the enzyme. The purpose of these simulations is to better learn about the function of Pin1 by modeling the conformational dynamics involved in its allosteric activation.

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Human Pin1

A peptidyl prolyl isomerase involved in cell signaling processes.

Human Pin1 is a protein crucial for regulating cellular processes. It acts as an enzyme that modifies other proteins by changing their shape. This modification influences how cells communicate and respond to signals. In cancer, Pin1 plays a role in the uncontrolled growth of tumor cells, making it a potential target for new therapies.

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Peptidyl prolyl isomerase (PPI)

Peptidyl prolyl isomerase

A type of enzyme that catalyzes the interconversion between cis and trans isomers of proline residues in proteins. This process is essential for proper protein folding and function.

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Phosphorylated serines

Serine amino acids that have been chemically modified by the addition of a phosphate group.

Phosphorylation is a common way for cells to regulate protein function. When a phosphate group is attached to serine residues on proteins, it can change their shape and activity. This process is involved in many cellular processes, including signaling, metabolism, and DNA replication.

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Threonines

An essential amino acid found in proteins.

Threonine is one of the 20 amino acids that make up proteins. It plays a role in protein structure and function, and can be modified by cells through phosphorylation.

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Cis/trans isomerization

The interconversion between two isomers of a molecule.

Proteins can exist in different shapes, called conformations. Cis/trans isomerization is a process where a protein changes its shape by flipping a specific bond. This can affect how the protein interacts with other molecules.

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Allosteric activation

A type of protein regulation where binding of a molecule to one site on the protein affects its activity at another site.

Allosteric activation is a way for cells to fine-tune enzyme activity. Binding of a molecule, called an allosteric effector, to a specific site on an enzyme can increase its ability to catalyze a reaction.

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Conformational dynamics

The changes in shape and orientation of a molecule over time.

Proteins are not static structures; they constantly move and change shape. This flexibility is essential for their function. Conformational dynamics refers to the study of these movements.

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Simulations

Computer-based models that mimic real-world processes.

Simulations are used in various fields, including drug discovery, to understand complex systems. By creating computer models of molecules and their interactions, researchers can predict how they will behave.