3741478

Decoding allosteric regulation guiding acyl carrier protein-dependent biosynthesis

Date
August 24, 2022

Acyl carrier proteins (ACPs) are involved in primary and secondary metabolic pathways, including the fatty acid biosynthesis that is required for all domains of life. This single protein must deliver pathway intermediates to the appropriate enzyme, distinguishing between a multitude of possible intermediate-enzyme combinations. The intermediate is delivered to the active site of enzymes through a large conformational change termed “chain flipping.” Whether chain flipping is a stochastic or regulated process has remained a mystery. We have combined the techniques of probe development, protein NMR, molecular dynamic simulations, and protein-protein docking simulations to decipher the rules associated with metabolite identity and enzyme activity in ACP dependent pathways. This study provides the first clear evidence for an allosteric regulation mechanism in any ACP dependent pathway, demonstrating that when the substrate interacts with the interior helical bundle, it confers structural changes to the exterior, which are recognized by enzymes via protein-protein interactions; presenting a new paradigm for understanding these biosynthetic pathways.

Presenter

Speaker Image for Michael Burkart
Professor, Chemistry and Biochemistry, University of California San Diego

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