RESEARCH: CANCER
FOLDING PROJECT #12478 PROFILE

Pin1 is a protein important for cell signals and cancer treatment. It changes shape to activate when it finds specific parts on other proteins. This project uses computer models to understand how Pin1 works.

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 peptides.

Peptidyl prolyl isomerases (PPIs) are a type of enzyme that plays a crucial role in protein folding and function. They specifically act on proline residues within proteins, changing their shape from cis to trans or vice versa. This process is essential for proper protein structure and activity.

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PPI

Peptidyl Prolyl Isomerase

PPI stands for Peptidyl Prolyl Isomerase. It's a type of enzyme that helps proteins fold correctly by changing the shape of proline residues.

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Cancer therapeutics

Treatments used to fight cancer.

Cancer therapeutics are medications and therapies designed to treat cancer. This includes a wide range of approaches, such as chemotherapy, targeted therapy, immunotherapy, and radiation.

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Phosphorylated

Having a phosphate group attached to it.

Phosphorylation is a common process in cells where a phosphate group is added to a molecule. This can change the molecule's shape and function, often acting as a switch to turn processes on or off.

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Serines

A type of amino acid.

Serines are one of the 20 standard amino acids that make up proteins. They have a hydroxyl group attached to their side chain, which can be involved in various chemical reactions.

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Threonines

A type of amino acid.

Threonines are another of the 20 standard amino acids found in proteins. They also have a hydroxyl group on their side chain, similar to serines.

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Cis/trans isomerization

The process of changing the shape of a molecule by flipping its bonds.

Cis/trans isomerization is a type of chemical transformation where a molecule's shape changes. Imagine a double bond in a molecule – it can exist in two forms: cis (atoms on the same side) or trans (atoms on opposite sides). This flipping back and forth is called isomerization.

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Allosteric activation

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

Allosteric activation is like having a control switch on an enzyme. When a specific molecule binds to a certain spot (the allosteric site), it changes the shape of the enzyme, making it more active and able to perform its job.

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Conformational dynamics

The movement and changes in shape of molecules.

Conformational dynamics refer to the constant jiggling and shifting of molecules. This movement is crucial for proteins, as it allows them to perform their tasks efficiently.