Skip to Main content Skip to Navigation
Journal articles

Conformational flexibility of coenzyme A and its impact on the post‐translational modification of acyl carrier proteins by 4′‐phosphopantetheinyl transferases

Abstract : One central question surrounding the biosynthesis of fatty acids and polyketide-derived natural products is how the 4 0-phosphopantetheinyl transferase (PPTase) interrogates the essential acyl carrier protein (ACP) domain to fulfill the initial activation step. The triggering factor of this study was the lack of structural information on PPTases at physiological pH, which could bias our comprehension of the mechanism of action of these important enzymes. Structural and functional studies on the family II PPTase PptAb of Mycobacterium abscessus show that pH has a profound effect on the coordination of metal ions and on the conformation of endogenously bound coenzyme A (CoA). The observed conformational flexibility of CoA at physiological pH is accompanied by a disordered 4 0-phosphopantetheine (Ppant) moiety. Finally, structural and dynamical information on an isolated mycobacterial ACP domain, in its apo form and in complex with the activator PptAb, suggests an alternate mechanism for the post-translational modification of modular megasynthases.
Complete list of metadata

https://hal.archives-ouvertes.fr/hal-02950584
Contributor : Lionel Mourey <>
Submitted on : Tuesday, November 24, 2020 - 10:08:40 AM
Last modification on : Monday, March 29, 2021 - 3:16:02 PM
Long-term archiving on: : Thursday, February 25, 2021 - 7:15:12 PM

File

nguyen-febsj20.pdf
Publisher files allowed on an open archive

Identifiers

Collections

Citation

Minh Chau Nguyen, Olivier Saurel, Coralie Carivenc, Sabine Gavalda, Stéphane Saitta, et al.. Conformational flexibility of coenzyme A and its impact on the post‐translational modification of acyl carrier proteins by 4′‐phosphopantetheinyl transferases. FEBS Journal, Wiley, 2020, 287, pp.4729 - 4746. ⟨10.1111/febs.15273⟩. ⟨hal-02950584⟩

Share

Metrics

Record views

46

Files downloads

62