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Conformational flexibility of coenzyme A and its impact on the post‐translational modification of acyl carrier proteins by 4′‐phosphopantetheinyl transferases
Author(s) -
Nguyen Minh Chau,
Saurel Olivier,
Carivenc Coralie,
Gavalda Sabine,
Saitta Stéphane,
Tran Mai Phuong,
Milon Alain,
Chalut Christian,
Guilhot Christophe,
Mourey Lionel,
Pedelacq JeanDenis
Publication year - 2020
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.15273
Subject(s) - coenzyme a , moiety , acyl carrier protein , cofactor , biochemistry , enzyme , chemistry , polyketide , activator (genetics) , stereochemistry , posttranslational modification , transferase , biology , biosynthesis , reductase , receptor
One central question surrounding the biosynthesis of fatty acids and polyketide‐derived natural products is how the 4′‐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′‐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.