RESEARCH: CANCER
FOLDING PROJECT #17909 PROFILE

This project looks at how different proteins change shape when they encounter their specific 'food source'. Some enzymes are picky eaters, while others can handle a wider variety. By studying these shapes, we hope to learn how proteins evolve to recognize different targets without needing 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.

---

substrate specificity

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

Substrate specificity describes how well an enzyme works with a specific molecule. It's important because enzymes are like tiny machines that carry out chemical reactions in our bodies, and each enzyme is designed to work best with certain molecules.

---

acyltransferase

An enzyme that catalyzes the transfer of an acyl group (R-CO-) from one molecule to another.

Acyltransferases are enzymes that move small chemical groups called acyl groups between molecules. They are essential for many biological processes, such as building and breaking down fats.

---

gene expression

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

Gene expression is how our genes are turned on and off. It's the process of making proteins based on the instructions in our DNA.

---

cancer development

The multi-step process by which normal cells transform into cancerous cells.

Cancer development is a complex process where healthy cells start to grow and divide uncontrollably. This can lead to the formation of tumors and spread of cancer.

---

sequence identity

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

Sequence identity measures how similar two protein sequences are. It helps scientists understand evolutionary relationships and protein function.

---

topology

The overall three-dimensional arrangement of a molecule or protein.

Topology describes the shape and structure of molecules. For proteins, it helps us understand how they fold into functional shapes.

---

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.

---

substrate permissiveness

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

Substrate permissiveness means that an enzyme can work with many different molecules. This is important for enzymes that need to be versatile and adapt to changing conditions.