Evidence map›Paper›PMID 39886071›Full record

ArticleBiochemistry and biophysics reports2025

Human citrate synthase kinetic simulation to fit rapid, direct, and thiol probe coupled kinetic data.

Noah Shackelford, Zach Zavodny, Samantha Schindler, Nathan Fancher, Allen A Thomas, Michael A Moxley

Abstract read

In one paragraph

Article in Biochemistry and biophysics reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

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0cells of the map it votes in

1citing papers in PubMed

–field-weighted citation impact

1 · What the graph read from it

What it found

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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

Human Citrate Synthase Post-Translational Modification Mimics and Molecular Dynamic Simulations Demonstrate Attenuation of Acetyl-CoA/CoA Binding.Proteins · 2026
Article

4 · The record

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PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors.

Noah ShackelfordDepartment of Chemistry, University of Nebraska at Kearney, USA.

Zach ZavodnyDepartment of Chemistry, University of Nebraska at Kearney, USA.

Samantha SchindlerDepartment of Chemistry, University of Nebraska at Kearney, USA.

Nathan FancherDepartment of Chemistry, University of Nebraska at Kearney, USA.

Allen A ThomasDepartment of Chemistry, University of Nebraska at Kearney, USA.

Michael A MoxleyDepartment of Chemistry, University of Nebraska at Kearney, USA.

Funding

UNMC Structural Biology CoreP20GM103427 · NIGMS · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI PAUL L SORGEN · 2012 to 2026

$59.2M

Pyruvate Dehydrogenase Complex Activation as a Strategy to Ameliorate Metabolic DiseaseR15GM152925 · NIGMS · UNIVERSITY OF NEBRASKA KEARNEY · PI MOXLEY, MICHAEL A · 2023 to 2023

$403k

NIGMS NIH HHS P20 GM103427NIGMS NIH HHS R15 GM152925

6 · The paper itself

Abstract

Human citrate synthase (hCS) was kinetically characterized through full progress curve kinetic modelling using kinetic simulation, global fitting of the direct AcCoA to CoA transition, and a coupled thiol probe reaction to better determine the kinetics with low substrate concentration. Our analysis provides one of the most rigorous kinetic analyses of any citrate synthase ruling out the need to invoke complex cooperative mechanisms to explain progress curve data. Furthermore, we collected and modeled stopped-flow pH-dependent kinetic data with CoA and popular thiol probes such as Ellman's reagent (DTNB) and 4,4'-Dithiodipyridine (DPS), providing the opportunity for detailed kinetic simulations using these thiol probes with CoA producing enzymes. Global fitting suggests that the DPS/CoA bimolecular rate constant increased 100-fold via protonation of the pyridine ring (pKa = 5.2), quantifying its kinetic advantage relative to DTNB. To explore the kinetic effects of polar substituents on the pyridine ring, we synthesized three different DPS analogs by adding either an alcohol, amine, or carboxylic acid moiety to the pyridine ring. Of these, the alcohol group provided the most similar kinetic characteristics to DPS but greatly increases thiol probe polarity offering an alternative to DPS.

Indexed as

Citrate synthaseEnzyme kineticsGlobal fittingKinetic simulationThiol probe

Identifiers

PMID39886071

DOI10.1016/j.bbrep.2025.101914

PMCPMC11780148

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LicenceCC BY-NC-ND

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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.