RESEARCH: CANCER
FOLDING PROJECT #17908 PROFILE

This project studies how enzymes called acyltransferases recognize different molecules. These enzymes have a flexible loop that changes shape when it binds to a molecule, allowing them to specialize in attaching specific tags to various targets. By comparing these loops, researchers hope to understand how proteins evolve to perform diverse functions without needing identical amino acid sequences.

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

Large biomolecules essential for various biological functions.

Proteins are the workhorses of cells, carrying out a vast array of functions. They are complex molecules made up of chains of amino acids that fold into unique shapes, allowing them to perform specific tasks such as catalyzing reactions, transporting molecules, and providing structural support.

acyltransferase

An enzyme that catalyzes the transfer of an acyl group (e.g., fatty acid) to a molecule.

Acyltransferases are enzymes that play crucial roles in various metabolic processes by transferring acyl groups from one molecule to another. This transfer is important for building and breaking down lipids, synthesizing hormones, and regulating gene expression.

substrate specificity

The ability of an enzyme to selectively bind and catalyze a specific reaction with its substrate.

Substrate specificity refers to the unique ability of enzymes to recognize and interact with specific molecules called substrates. This selectivity is crucial for regulating biochemical reactions and maintaining cellular order.

homology modeling

A computational method to predict the 3D structure of a protein based on its amino acid sequence and known structures of similar proteins.

Homology modeling is a powerful technique used to predict the three-dimensional shape of proteins. It relies on comparing the amino acid sequence of an unknown protein with those of proteins whose structures are already known.