RESEARCH: CANCER
FOLDING PROJECT #18909 PROFILE

Lasso peptides are tiny, unique proteins with potential as new drugs. They form a loop shape, and scientists want to understand how this happens. This project will use computer simulations to see how lasso peptide cyclase, an enzyme, helps create the loop in lasso peptides.

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

Lasso peptides are ribosomally synthesized and post-translationally modified peptide (RiPP) natural products that display a unique lariat-like, threaded conformation.

Some lasso peptides have been shown to bind human cell-surface receptors and exhibit anticancer properties, while others display antibacterial or antiviral bioactivities.

So studies on the lasso peptide synthesis will significantly facilitate the discovery and application of new drugs. Specifically, previous studies show that the unique lasso topology is formed by a macrolactam ring that is threaded by the C-terminal tail.

While not proven yet, the threading cannot occur after the ring formation.

The general proposed mechanism is that lasso peptide first form a prefolded lariat-like structure, then lasso peptide cyclase catalyzes the ring closure achieved by an isopeptide bond formed between the N-terminal α-amino group of a glycine, alanine, serine, or cysteine and the carboxylic acid side chain of an aspartate or glutamate, which can be located at positions 7, 8, or 9 of the amino acid sequence.

However, the detailed function of lasso peptide cyclase and the molecular mechanism of the whole lasso peptide cyclization process are not clear.

Therefore, in this study, we will perform Molecular Dynamic simulations for the system of lasso peptide with cyclase enzyme to explore lasso peptide cyclization mechanism.

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Lasso peptides

Ribosomally synthesized and post-translationally modified peptides with a unique lariat-like conformation.

Lasso peptides are a type of naturally occurring molecule made by bacteria. They have a special ring structure that allows them to bind to other molecules in the body. Scientists are studying lasso peptides because they might be useful as new drugs to treat diseases like cancer.

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Ribosomally synthesized

Synthesized by ribosomes, the cellular machinery responsible for protein production.

Ribosomes are tiny factories inside cells that build proteins. When something is 'ribosomally synthesized,' it means it was made by a ribosome.

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Post-translationally modified

Modifications made to a protein after it has been synthesized by ribosomes.

Proteins are often changed after they're made. 'Post-translationally modified' means these changes happen after the protein is first built.

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RiPP

Ribosomally synthesized and post-translationally modified peptides

RiPP stands for ribosomally synthesized and post-translationally modified peptides. These are special types of molecules made by bacteria that have lots of potential uses in medicine.

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Macrolactam ring

A large cyclic amide formed by the reaction of a carboxylic acid group with an amino group.

A macrolactam ring is like a big, round molecule made from two parts of a protein. This ring structure is important for lasso peptides' ability to do their job.

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Lasso peptide cyclase

An enzyme that catalyzes the formation of the macrolactam ring in lasso peptides.

Lasso peptide cyclase is a special protein that helps lasso peptides form their unique ring structure. This process is crucial for making lasso peptides work.

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Molecular Dynamic simulations

Computer simulations that model the movement and interactions of molecules over time.

Molecular Dynamic simulations are like computer games for molecules. Scientists use them to understand how things work at a tiny level, like how proteins move and interact.