RESEARCH: CANCER
FOLDING PROJECT #17910 PROFILE

This project looks at how enzymes called acyltransferases change shape when they bind to different molecules. These enzymes are important for things like gene activity and cancer, but they don't all have the same building blocks. By studying their movements, scientists hope to understand how these enzymes evolved to recognize specific targets without needing identical 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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substrate specificity

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

Substrate specificity refers to an enzyme's ability to recognize and bind to specific molecules called substrates. This selectivity is crucial for biological processes as it ensures that enzymes catalyze the desired reactions without affecting other molecules in the cell.

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acyltransferase

An enzyme that catalyzes the transfer of an acyl group (an organic molecule containing a carbonyl group) from one molecule to another.

Acyltransferases are enzymes responsible for transferring acyl groups between molecules. This process plays a vital role in various metabolic pathways, including lipid synthesis, signal transduction, and protein modification.

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organismal evolutionary stage

The developmental point or stage of an organism within its evolutionary history.

Organismal evolutionary stage refers to the position an organism holds in its evolutionary lineage. Different stages reflect varying levels of complexity and adaptation to environmental pressures throughout the organism's history.

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gene expression

The process by which information encoded in a gene is used to synthesize functional products, such as proteins or RNA molecules.

Gene expression is the fundamental process by which genetic information is converted into functional molecules. It involves two main steps: transcription, where DNA is copied into RNA, and translation, where RNA is used to build proteins.

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cancer development

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

Cancer development is a complex process involving genetic mutations and alterations in cellular signaling pathways. These changes allow cells to grow uncontrollably, invade surrounding tissues, and spread throughout the body.

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sequence identity

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

Sequence identity is a measure of similarity between protein sequences. A higher sequence identity indicates greater evolutionary relatedness between the proteins.

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topology

The three-dimensional arrangement of atoms and molecules within a protein.

Protein topology refers to the overall spatial structure of a protein molecule. Understanding protein topology is crucial for comprehending its function and interactions with other molecules.

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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 regions within proteins that lack a stable conformation. These loops play important roles in protein function by mediating interactions with other molecules and adapting to changing cellular environments.

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substrate permissiveness

The ability of an enzyme to accept a wide range of substrates.

Substrate permissiveness refers to the broad spectrum of molecules an enzyme can effectively catalyze. Enzymes with high substrate permissiveness are versatile and can participate in multiple metabolic pathways.