RESEARCH: CANCER
FOLDING PROJECT #15302 PROFILE

This project explores how a special enzyme called ProcM chooses specific molecules to modify. By using computer simulations, scientists will try to understand how ProcM works at a very detailed level. This knowledge could help us create new drugs and therapies in the future.

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

Lanthipeptides are a class of ribosomally synthesized and post-translationally modified peptides (RiPPs) produced from precursor peptides through dehydration and cyclization reactions.

They exhibit a broad range of bioactivities, including anticancer, antimicrobial, antiviral, and antiallodynic effects.

ProcM, a class II lanthipeptide synthetase, is notable for its high substrate tolerance.

Remarkably, this single enzyme can catalyze the cyclization of a diverse array of substrates with high fidelity—an ability that has been extensively leveraged in the bioengineering of novel lanthipeptides.

Despite this, the molecular mechanism by which ProcM determines the site-selectivity of its substrates remains unclear.

In this study, we aim to perform atomic-level molecular dynamics (MD) simulations of the wild-type (WT) and Variant ProcM–ProcA3.3 complexes to investigate the basis of ProcM's site-selectivity.

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Lanthipeptides

A class of ribosomally synthesized and post-translationally modified peptides.

Lanthipeptides are a type of antibiotic produced by bacteria. They are made up of smaller peptide chains that have been chemically modified to become effective against other microorganisms. Lanthipeptides have a wide range of applications in medicine, including the treatment of bacterial infections and the development of new drugs.

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Ribosomally synthesized and post-translationally modified peptides (RiPPs)

Ribosomally synthesized and post-translationally modified peptides (RiPPs)

RiPPs are a class of antimicrobial peptides that are produced by ribosomes. After synthesis, they undergo chemical modifications to become active against bacteria.

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ProcM

ProcM, a class II lanthipeptide synthetase

ProcM is an enzyme that plays a role in the synthesis of lanthipeptides. It catalyzes the cyclization of precursor peptides to form active antimicrobial molecules.

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Site-selectivity

The ability of an enzyme to bind and modify specific substrates at particular sites.

Site-selectivity refers to the ability of enzymes to choose specific locations on a molecule for modification. This is crucial for many biological processes, including the production of antibiotics.

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Molecular Dynamics (MD) Simulations

Molecular Dynamics (MD) Simulations

MD simulations are computer-based models that simulate the movement and interactions of atoms and molecules over time. They are used to study the structure and function of biological systems.

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Variant ProcM–ProcA3.3 Complexes

Modified versions of the ProcM enzyme that have been combined with a protein called ProcA3.3.

Variants are modified versions of existing proteins. In this case, researchers have created variants of ProcM and combined them with another protein called ProcA3.3 to study how they interact and function.