Open AccessPhosphodianion Activation of Enzymes for Catalysis of Central Metabolic Reactions
Author(s) -
Patrick Fernandez,
Richard W. Nagorski,
Judith R. Cristobal,
Tina L. Amyes,
John P. Richard
Publication year - 2021
Publication title -
journal of the american chemical society
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.115
H-Index - 612
eISSN - 1520-5126
pISSN - 0002-7863
DOI - 10.1021/jacs.0c13423
Subject(s) - chemistry , triosephosphate isomerase , dehydrogenase , enzyme , isomerase , enzyme kinetics , biochemistry , stereochemistry , substrate (aquarium) , dihydroxyacetone phosphate , transaldolase , enzyme catalysis , active site , glycolysis , pentose phosphate pathway , oceanography , geology
The activation barriers Δ G ⧧ for k cat / K m for the reactions of whole substrates catalyzed by 6-phosphogluconate dehydrogenase, glucose 6-phosphate dehydrogenase, and glucose 6-phosphate isomerase are reduced by 11-13 kcal/mol by interactions between the protein and the substrate phosphodianion. Between 4 and 6 kcal/mol of this dianion binding energy is expressed at the transition state for phosphite dianion activation of the respective enzyme-catalyzed reactions of truncated substrates d-xylonate or d-xylose. These and earlier results from studies on β-phosphoglucomutase, triosephosphate isomerase, and glycerol 3-phosphate dehydrogenase define a cluster of six enzymes that catalyze reactions in glycolysis or of glycolytic intermediates, and which utilize substrate dianion binding energy for enzyme activation. Dianion-driven conformational changes, which convert flexible open proteins to tight protein cages for the phosphorylated substrate, have been thoroughly documented for five of these six enzymes. The clustering of metabolic enzymes which couple phosphodianion-driven conformational changes to enzyme activation suggests that this catalytic motif has been widely propagated in the proteome.