Allosteric regulation alters carrier domain translocation in pyruvate carboxylase

Pyruvate carboxylase (PC) catalyzes the ATP-dependent carboxylation of pyruvate to oxaloacetate. The reaction occurs in two separate catalytic domains, coupled by the long-range translocation of a biotinylated carrier domain (BCCP). Here, we use a series of hybrid PC enzymes to examine multiple BCCP...

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Veröffentlicht in:Nature communications 2018-04, Vol.9 (1), p.1384-13, Article 1384
Hauptverfasser: Liu, Yumeng, Budelier, Melissa M., Stine, Katelyn, St. Maurice, Martin
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Sprache:eng
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Zusammenfassung:Pyruvate carboxylase (PC) catalyzes the ATP-dependent carboxylation of pyruvate to oxaloacetate. The reaction occurs in two separate catalytic domains, coupled by the long-range translocation of a biotinylated carrier domain (BCCP). Here, we use a series of hybrid PC enzymes to examine multiple BCCP translocation pathways in PC. These studies reveal that the BCCP domain of PC adopts a wide range of translocation pathways during catalysis. Furthermore, the allosteric activator, acetyl CoA, promotes one specific intermolecular carrier domain translocation pathway. These results provide a basis for the ordered thermodynamic state and the enhanced carboxyl group transfer efficiency in the presence of acetyl CoA, and reveal that the allosteric effector regulates enzyme activity by altering carrier domain movement. Given the similarities with enzymes involved in the modular synthesis of natural products, the allosteric regulation of carrier domain movements in PC is likely to be broadly applicable to multiple important enzyme systems. Carrier domain enzymes accomplish catalysis by physically transporting intermediates long distances between remote active sites. Here the authors describe a wide range of catalytically productive translocation events during catalysis by pyruvate carboxylase and suggest a basis for its allosteric activation.
ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-018-03814-8