RESEARCH: CANCER
FOLDING PROJECT #17905 PROFILE

This project studies how proteins called acyltransferases change shape to recognize different molecules they work with. Acyltransferases are important for things like gene activity and cancer, and the study focuses on a flexible part of these proteins that seems to control their ability to bind to various targets.

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 composed of amino acids.

Proteins are the workhorses of cells, carrying out a vast array of functions. They are made up of chains of amino acids folded into specific 3D shapes. These shapes allow proteins to interact with other molecules and perform their diverse roles in living organisms.

substrate specificity

The ability of an enzyme to preferentially bind and act upon a particular substrate.

Substrate specificity refers to the selective nature of enzymes. Each enzyme has evolved to recognize and interact with specific molecules called substrates. This specificity is crucial for controlling biochemical reactions within cells.

acyltransferase

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

Acyltransferases are a crucial class of enzymes involved in various metabolic processes. They facilitate the transfer of acyl groups, which are chemical fragments containing an oxygen-linked carbon chain, between different molecules.

gene expression

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

Gene expression is the fundamental process by which cells translate genetic information into functional molecules. It involves two main steps: transcription (DNA to RNA) and translation (RNA to protein). This process allows cells to produce the proteins they need to function.

cancer

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

Cancer is a complex group of diseases involving the abnormal proliferation of cells. These cancerous cells can invade surrounding tissues and spread to other parts of the body. Cancer development is influenced by genetic mutations, environmental factors, and lifestyle choices.