RESEARCH: CANCER
FOLDING PROJECT #17904 PROFILE

This project looks at how different types of enzymes called acyltransferases recognize and bind to specific molecules. Acyltransferases are important for many processes in our bodies, like gene expression and cancer development. The researchers are studying how the shape and flexibility of a loop region within these enzymes affects their ability to bind to different molecules. Understanding this could help us design new drugs that target specific enzymes.

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.

protein

A large biomolecule consisting of chains of amino acids.

Proteins are the workhorses of cells, carrying out a vast array of functions essential for life. They are made up of building blocks called amino acids, linked together in long chains. The sequence and folding of these chains determine the protein's unique shape and function.

substrate

A substance acted upon by an enzyme.

In biochemistry, a substrate is the molecule that an enzyme acts upon. The enzyme catalyzes a chemical reaction, converting the substrate into a product.

acyltransferase

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

Acyltransferases are a class of enzymes that play a crucial role in various metabolic processes. They facilitate the transfer of acyl groups, which are chains of carbon atoms attached to a carbonyl group, between molecules.

gene expression

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

Gene expression is the fundamental process by which cells convert the genetic information stored in DNA into functional products like proteins. It involves two main steps: transcription and translation.

cancer

A group of diseases characterized by the uncontrolled growth and spread of abnormal cells.

Cancer is a complex group of diseases marked by the uncontrolled proliferation of abnormal cells. These cells can invade surrounding tissues and spread to other parts of the body, causing significant damage.