RESEARCH: CANCER
FOLDING PROJECT #17907 PROFILE

This project looks at how enzymes called acyltransferases change shape when they bind to different molecules. These enzymes are important for things like gene activity and cancer, but they don't all recognize the same molecules. By studying how their flexible parts move, scientists hope to understand how these enzymes evolved to be specific without having identical building blocks.

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

Understanding the molecular basis of substrate specificity for a given protein family is fundamental for the biophysical study of any metabolic process and related molecule design.

In this project, we model the apo and holo dynamics of acyltransferase enzymes demonstrating variable substrate specificity and organismal evolutionary stage.

Human acyltransferase activity is generally implicated in gene expression and cancer development.

Averaging ~18-25 sequence identity within their family, our selected acyltransferase enzymes maintain a remarkably conserved topology, where the front and back domains of these proteins form a doughnut-like shape bridged by an ~50 residue intrinsically disordered loop (IDL).

Sequence-based analyses suggest that some correlation exists between the extent of disorder in this IDL region and the extent of demonstrated substrate permissiveness by the respective enzyme.

By comparing loop dynamics in response to substrate recognition between the different modeled proteins, our goal is to offer fundamental insights into how soluble proteins can evolve substrate specificity without converging to a conserved amino acid sequence.

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protein family

A group of proteins with similar structures and functions.

Proteins belonging to the same family share common characteristics like structure and function. They often evolve from a shared ancestor.

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substrate specificity

The ability of an enzyme to selectively bind and act upon a specific substrate.

Each enzyme has a unique ability to work with certain molecules called substrates. This specificity is crucial for biological processes.

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acyltransferase

An enzyme that catalyzes the transfer of an acyl group from one molecule to another.

Acyltransferases are enzymes that facilitate the movement of acyl groups (chains of carbon and hydrogen atoms) between molecules. They play essential roles in various metabolic pathways.

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gene expression

The process by which information from a gene is used to synthesize a functional product, such as a protein.

Gene expression is how our DNA instructions are used to create the molecules that build and run our bodies. It's a fundamental process in all living organisms.

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cancer development

The process by which normal cells transform into cancerous cells.

Cancer development is a complex process involving changes in our DNA that lead to uncontrolled cell growth and spread. It's a major cause of death worldwide.

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sequence identity

The percentage of identical amino acid residues between two protein sequences.

Sequence identity helps us understand how similar different proteins are. A higher percentage means they're more closely related.

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intrinsically disordered loop (IDL)

A region of a protein that lacks a defined three-dimensional structure.

Intrinsically disordered loops (IDLs) are flexible parts of proteins that can change shape and interact with other molecules. They play important roles in protein function.

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substrate permissiveness

The ability of an enzyme to act upon a wide range of substrates.

Substrate permissiveness means that an enzyme can work with multiple different molecules. This flexibility is important for adapting to changing conditions.