In <i>E. coli</i>, the acyltransferase (AT), FabD, initiates fatty acid biosynthesis by charging the acyl carrier protein (ACP), AcpP, with malonyl-CoA. In order to catalyze this chemical transformation, FabD, must form a complex with AcpP. This paper highlights the computational aspects of a multidisciplinary study that utilized structural, chemical, and computational biology techniques to resolve the protein-protein interactions that are required for catalysis. Molecular dynamics simulations –in agreement with experimental findings– reveal a robust and dynamic AcpP●FabD interface. Simulations also resolve key subdomain motions that govern AT function and substrate-induced reorganization of FabD’s active site. These findings establish the mechanism of action of FabD and clarify the molecular basis of ACP●AT molecular recognition, providing insights that may inform efforts to (re-)engineer AT-dependent biosynthetic pathways.

Dynamical rationale for the robustness of FabD, an acyltransferase involved in <i>E. coli </i>fatty acid biosynthesis

ACS Spring Meeting 2021

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Dynamical rationale for the robustness of FabD, an acyltransferase involved in E. coli fatty acid biosynthesis