ArticleJournal of the American Chemical Society2015
Enzyme architecture: optimization of transition state stabilization from a cation-phosphodianion pair.
Article in Journal of the American Chemical Society, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 34 citations in OpenAlex.
- The Role of Protein Side Chains in Enzyme-Activating Conformational Changes: Lessons from Studies on Variant Enzymes.Chemical reviews · 2025Review
- Glycerol 3-Phosphate Dehydrogenase Catalyzed Hydride Transfer: Enzyme Activation by Cofactor Pieces.Biochemistry · 2024Article
- Glycerol 3-Phosphate Dehydrogenase: Role of the Protein Conformational Change in Activation of a Readily Reversible Enzyme-Catalyzed Hydride Transfer Reaction.Biochemistry · 2024Article
- Triosephosphate Isomerase: The Crippling Effect of the P168A/I172A Substitution at the Heart of an Enzyme Active Site.Biochemistry · 2023Article
- Utilization of Cofactor Binding Energy for Enzyme Catalysis: Formate Dehydrogenase-Catalyzed Reactions of the Whole NAD Cofactor and Cofactor Pieces.Biochemistry · 2023Article
- Kinetics and mechanism for enzyme-catalyzed reactions of substrate pieces.Methods in enzymology · 2023Article
- Glycerol-3-Phosphate Dehydrogenase: The K120 and K204 Side Chains Define an Oxyanion Hole at the Enzyme Active Site.Biochemistry · 2022Article
- An Enzyme with High Catalytic Proficiency Utilizes Distal Site Substrate Binding Energy to Stabilize the Closed State but at the Expense of Substrate Inhibition.ACS catalysis · 2022Article
- Linear Free Energy Relationships for Enzymatic Reactions: Fresh Insight from a Venerable Probe.Accounts of chemical research · 2021Review
- Hydride Transfer Catalyzed by Glycerol Phosphate Dehydrogenase: Recruitment of an Acidic Amino Acid Side Chain to Rescue a Damaged Enzyme.Biochemistry · 2020Article
- Modeling the Role of a Flexible Loop and Active Site Side Chains in Hydride Transfer Catalyzed by Glycerol-3-phosphate Dehydrogenase.ACS catalysis · 2020Article
- The Organization of Active Site Side Chains of Glycerol-3-phosphate Dehydrogenase Promotes Efficient Enzyme Catalysis and Rescue of Variant Enzymes.Biochemistry · 2020Article
- Rosy Beginnings: Studying Peroxisomes inFrontiers in cell and developmental biology · 2020Review
- The role of ligand-gated conformational changes in enzyme catalysis.Biochemical Society transactions · 2019Review
- Role of the Carboxylate in Enzyme-Catalyzed Decarboxylation of Orotidine 5'-Monophosphate: Transition State Stabilization Dominates Over Ground State Destabilization.Journal of the American Chemical Society · 2019Article
- Human Glycerol 3-Phosphate Dehydrogenase: X-ray Crystal Structures That Guide the Interpretation of Mutagenesis Studies.Biochemistry · 2019Article
- Primary Deuterium Kinetic Isotope Effects: A Probe for the Origin of the Rate Acceleration for Hydride Transfer Catalyzed by Glycerol-3-Phosphate Dehydrogenase.Biochemistry · 2018Article
- Enzyme Architecture: The Role of a Flexible Loop in Activation of Glycerol-3-phosphate Dehydrogenase for Catalysis of Hydride Transfer.Biochemistry · 2018Article
- Investigation of the proton relay system operative in human cystosolic aminopeptidase P.PloS one · 2018Article
- A reevaluation of the origin of the rate acceleration for enzyme-catalyzed hydride transfer.Organic & biomolecular chemistry · 2017Review
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The side chain cation of R269 lies at the surface of l-glycerol 3-phosphate dehydrogenase (GPDH) and forms an ion pair to the phosphodianion of substrate dihydroxyacetone phosphate (DHAP), which is buried at the nonpolar protein interior. The R269A mutation of GPDH results in a 110-fold increase in K(m) (2.8 kcal/mol effect) and a 41,000-fold decrease in k(cat) (6.3 kcal/mol effect), which corresponds to a 9.1 kcal/mol destabilization of the transition state for GPDH-catalyzed reduction of DHAP by NADH. There is a 6.7 kcal/mol stabilization of the transition state for the R269A mutant GPDH-catalyzed reaction by 1.0 M guanidinium ion, and the transition state for the reaction of the substrate pieces is stabilized by an additional 2.4 kcal/mol by their covalent attachment at wildtype GPDH. These results provide strong support for the proposal that GPDH invests the 11 kcal/mol intrinsic phosphodianion binding energy of DHAP in trapping the substrate at a nonpolar active site, where strong electrostatic interactions are favored, and obtains a 9 kcal/mol return from stabilizing interactions between the side chain cation and transition state trianion. We propose a wide propagation for the catalytic motif examined in this work, which enables strong transition state stabilization from enzyme-phosphodianion pairs.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.