Official Project Description
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.