RESEARCH: CANCER
FOLDING PROJECT #12477 PROFILE

Pin1 is a protein that helps control cell signals. It changes shape to activate when it binds to certain molecules. This project uses computer simulations to understand how Pin1 changes shape and gets activated, which could help us develop 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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Peptidyl prolyl isomerase

An enzyme that catalyzes the interconversion of cis and trans isomers of proline residues in peptide bonds.

Peptidyl prolyl isomerases (PPIs) are a class of enzymes that play a crucial role in protein folding and function. They specifically catalyze the isomerization of proline residues, which are common amino acids found in proteins. This isomerization process affects the shape and flexibility of proteins, influencing their interactions with other molecules and overall biological activity.

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PPI

Peptidyl Prolyl Isomerase

PPI stands for Peptidyl Prolyl Isomerase, a type of enzyme that catalyzes the conversion of cis and trans isomers of proline residues within proteins. This process is essential for proper protein folding and function.

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Cancer Therapeutics

Medical treatments aimed at preventing, inhibiting, or curing cancer.

Cancer therapeutics encompass a wide range of medical interventions designed to combat the growth and spread of cancer cells. This includes various therapies such as chemotherapy, radiation therapy, immunotherapy, and targeted drug therapies.

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Phosphorylated

Modified by the addition of a phosphate group.

Phosphorylation is a crucial process in cellular signaling where a phosphate group is attached to a molecule, typically a protein. This modification can alter the activity, shape, or interactions of the target molecule, influencing various cellular processes.

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Allosteric Activation

The process by which a molecule binds to a site on an enzyme other than the active site, inducing a conformational change that increases enzyme activity.

Allosteric activation is a type of enzyme regulation where a molecule, called an allosteric activator, binds to a specific site on the enzyme. This binding induces a change in the enzyme's shape, enhancing its ability to catalyze a reaction.

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Conformational Dynamics

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

Conformational dynamics refers to the continuous fluctuations and movements in the three-dimensional structure of molecules. This dynamic nature is essential for various biological processes, including protein folding, enzyme activity, and cellular signaling.