Open AccessDecoding allosteric regulation by the acyl carrier protein
Author(s) -
Terra Sztain,
Thomas G. Bartholow,
Lee DJ,
Lorenzo Casalino,
Andrew R. Mitchell,
Megan Young,
JiaNing Wang,
J. Andrew McCammon,
Michael D. Burkart
Publication year - 2021
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2025597118
Subject(s) - allosteric regulation , protein dynamics , enzyme , substrate (aquarium) , allosteric enzyme , biochemistry , protein engineering , biology , structural biology , biophysics , metabolic pathway , protein structure , acyl carrier protein , chemistry , microbiology and biotechnology , biosynthesis , ecology
Significance Acyl carrier proteins (ACPs) are involved in primary and secondary metabolic pathways, including the ubiquitous fatty acid biosynthesis, required for all domains of life. This single protein must deliver pathway intermediates to the appropriate enzyme, distinguishing between a myriad 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. This study provides evidence for an allosteric regulatory mechanism—demonstrating that substrates sequestered within the interior side of the four-helical ACP bundle confer structural changes to the exterior which are recognized by enzymes via protein–protein interactions—presenting a unique paradigm for understanding these biosynthetic pathways.