RESEARCH: CANCER
FOLDING PROJECT #17911 PROFILE

This project studies how enzymes called acyltransferases change shape to recognize different molecules. These enzymes are important for processes like gene expression and cancer. By looking at how the flexible part of these enzymes moves when it binds to molecules, scientists hope to understand how they evolved to have different specificities without needing identical amino acid sequences.

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 structure and function.

Protein families are groups of proteins that share common characteristics like structure and function. They often evolved from a common ancestor and play similar roles in biological processes.

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acyltransferase

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

Acyltransferases are a type of enzyme that help move chemical groups called acyl groups between molecules. They play important roles in processes like metabolism and cell signaling.

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substrate specificity

The ability of an enzyme to preferentially bind and catalyze a specific substrate.

Substrate specificity refers to how well an enzyme can work with a particular molecule (the substrate). Some enzymes are very picky, only working with one type of substrate, while others are more flexible.

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organismal evolutionary stage

The point in an organism's life cycle where it has evolved certain traits.

Organismal evolutionary stage describes where a species is in its evolutionary journey. Different stages are marked by specific adaptations and characteristics that help the organism survive in its environment.

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homology modeling

A computational method for predicting the three-dimensional structure of a protein based on its amino acid sequence and the known structures of related proteins.

Homology modeling is a way to predict the shape of a protein using information from similar proteins whose structures are already known. It's like using a blueprint to build a model.

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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 and unstructured parts of proteins. They often play important roles in interactions with other molecules.

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substrate permissiveness

The ability of an enzyme to catalyze a reaction with a variety of different substrates.

Substrate permissiveness describes how flexible an enzyme is in accepting different molecules as its fuel. Some enzymes are very picky, while others can work with a wider range of inputs.