Structure of Insoluble Rat Sperm Glyceraldehyde-3-phosphate Dehydrogenase (GAPDH) via Heterotetramer Formation with Escherichia coli GAPDH Reveals Target for Contraceptive Design*

@article{Frayne2009StructureOI,
  title={Structure of Insoluble Rat Sperm Glyceraldehyde-3-phosphate Dehydrogenase (GAPDH) via Heterotetramer Formation with Escherichia coli GAPDH Reveals Target for Contraceptive Design*},
  author={Jan Frayne and Abby Taylor and Gus Cameron and Andrea T. Hadfield},
  journal={The Journal of Biological Chemistry},
  year={2009},
  volume={284},
  pages={22703 - 22712}
}
Sperm glyceraldehyde-3-phosphate dehydrogenase has been shown to be a successful target for a non-hormonal contraceptive approach, but the agents tested to date have had unacceptable side effects. Obtaining the structure of the sperm-specific isoform to allow rational inhibitor design has therefore been a goal for a number of years but has proved intractable because of the insoluble nature of both native and recombinant protein. We have obtained soluble recombinant sperm glyceraldehyde-3… 
Structure and kinetic characterization of human sperm-specific glyceraldehyde-3-phosphate dehydrogenase, GAPDS.
TLDR
In the present study, overexpressed in Escherichia coli a highly soluble form of hGAPDS truncated at the N-terminus (hGAP DSΔN), and crystallized the homotetrameric enzyme in two ligand complexes to elucidate structural and kinetic features of h GAPDS that might provide insightful information towards inhibitor development.
Structural analyses to identify selective inhibitors of glyceraldehyde 3-phosphate dehydrogenase-S, a sperm-specific glycolytic enzyme.
TLDR
This study provides proof-of-principle evidence that GAPDHS can be selectively inhibited, causing significant reductions in sperm glycolysis and motility, and highlights the utility of structure-based drug design and support further exploration of GAPD HS, and perhaps other sperm-specific isozymes in the glyCOlytic pathway, as contraceptive targets.
A Novel Substrate-Binding Site in the X-ray Structure of an Oxidized E. coli Glyceraldehyde 3-Phosphate Dehydrogenase Elucidated by Single-Wavelength Anomalous Dispersion
Escherichia coli (E. coli), one of the most frequently used host for the expression of recombinant proteins, is often affected by the toxic effect of the exogenous proteins that is required to
A Novel Substrate-Binding Site in the X-ray Structure of an Oxidized E. coli Glyceraldehyde 3-Phosphate Dehydrogenase Elucidated by Single-Wavelength Anomalous Dispersion
Escherichia coli (E. coli), one of the most frequently used host for the expression of recombinant proteins, is often affected by the toxic effect of the exogenous proteins that is required to
Characterization and possible function of glyceraldehyde-3-phosphate dehydrogenase-spermatogenic protein GAPDHS in mammalian sperm
TLDR
GAPDHS is a sperm-specific glycolytic enzyme involved in energy production during spermatogenesis and sperm motility; its role in the sperm head is unknown but the potential role of this protein in the secondary sperm/oocyte binding is confirmed.
Sperm-Specific Glyceraldehyde-3-Phosphate Dehydrogenase–An Evolutionary Acquisition of Mammals
TLDR
GAPDS is much more stable compared to the somatic isoenzyme, perhaps due to the necessity of maintaining the enzyme function in the absence of protein expression, and its role in the development of certain pathologies, such as cancer and neurodegenerative diseases, is discussed.
Development and Implementation of a High Throughput Screen for the Human Sperm-Specific Isoform of Glyceraldehyde 3-Phosphate Dehydrogenase (GAPDHS)
TLDR
This assay was used to screen a diverse chemical library and identified fourteen small molecules that modulated the activity of recombinant purified GAPDHS with confirmed IC50 values ranging from 1.8 to 42 µM, indicating a robust assay for HTS.
Partial catalytic Cys oxidation of human GAPDH [version 1; peer review: awaiting peer review]
  • 2020
n-Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) Background catalyses the reversible NAD -dependent oxidative phosphorylation of n-glyceraldehyde-3-phosphate to 1,3-diphospho-n-glycerate in both
Partial catalytic Cys oxidation of human GAPDH.
TLDR
The modification induces no significant structural changes on the tetrameric enzyme, and only makes aspecific contacts to surface residues in the active site, in keeping with the hypothesis that the oxidising conditions of the secreted mammalian cell expression system result in HsGAPDH catalytic cysteine S-sulfonic acid modification and irreversible inactivation of the enzyme.
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