Influence of Oxidative Stress on Catalytic and Non-glycolytic Functions of Glyceraldehyde-3-phosphate Dehydrogenase

Muronetz, Vladimir I.; Melnikova, Aleksandra; Saso, Luciano; Schmalhausen, E.V.

doi:10.2174/0929867325666180530101057

Cited by 27 publications

(11 citation statements)

References 113 publications

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“…Under the osmotic stress conditions, the cellular metabolic reprogramming recruits the constitutive proteins for other cellular functions of necessity. Such multi-tasking proteins are called moonlighting proteins and GAPDH performs such functions under osmotic stress 55 .…”

Section: Discussionmentioning

confidence: 99%

Sperm preparedness and adaptation to osmotic and pH stressors relate to functional competence of sperm in Bos taurus

Lavanya

Archana

Swathi

et al. 2021

Sci Rep

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The adaptive ability of sperm in the female reproductive tract micromilieu signifies the successful fertilization process. The study aimed to analyze the preparedness of sperm to the prevailing osmotic and pH stressors in the female reproductive tract. Fresh bovine sperm were incubated in 290 (isosmotic-control), 355 (hyperosmotic-uterus and oviduct), and 420 (hyperosmotic-control) mOsm/kg and each with pH of 6.8 (uterus) and 7.4 (oviduct). During incubation, the changes in sperm functional attributes were studied. Sperm kinematics and head area decreased significantly (p < 0.05) immediately upon exposure to hyperosmotic stress at both pH. Proportion of sperm capacitated (%) in 355 mOsm/kg at 1 and 2 h of incubation were significantly (p < 0.05) higher than those in 290 mOsm media. The magnitude and duration of recovery of sperm progressive motility in 355 mOsm with pH 7.4 was correlated with the ejaculate rejection rate (R2 = 0.7). Using this information, the bulls were divided into good (n = 5) and poor (n = 5) osmo-adapters. The osmo-responsive genes such as NFAT5, HSP90AB1, SLC9C1, ADAM1B and GAPDH were upregulated (p < 0.05) in the sperm of good osmo-adapters. The study suggests that sperm are prepared for the osmotic and pH challenges in the female reproductive tract and the osmoadaptive ability is associated with ejaculate quality in bulls.

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Section: Discussionmentioning

confidence: 99%

Sperm preparedness and adaptation to osmotic and pH stressors relate to functional competence of sperm in Bos taurus

Lavanya

Archana

Swathi

et al. 2021

Sci Rep

View full text Add to dashboard Cite

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“…The most probable site for the oxidation is the C152 residue located in the catalytic region of the enzyme molecule. Oxidation of C152 causes an inactivation of GAPDH and the formation of intra-or inter-molecular disulfide bonds [64,65]. Another mechanism triggered by the oxidation of M46 on the GAPDH molecule, which also leads to enzyme denaturation and the formation of aggregates through disulfide bridges [66].…”

Section: Senescencementioning

confidence: 99%

Glyceraldehyde-3-phosphate Dehydrogenase Is a Multifaceted Therapeutic Target

2020

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Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a glycolytic enzyme whose role in cell metabolism and homeostasis is well defined, while its function in pathologic processes needs further elucidation. Depending on the cell context, GAPDH may bind a number of physiologically important proteins, control their function and correspondingly affect the cell’s fate. These interprotein interactions and post-translational modifications of GAPDH mediate its cytotoxic or cytoprotective functions in the manner of a Janus-like molecule. In this review, we discuss the functional features of the enzyme in cellular physiology and its possible involvement in human pathologies. In the last part of the article, we describe drugs that can be employed to modulate this enzyme’s function in some pathologic states.

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“…After the first rounds of refinement, an initial search for a possible transition state intermediate was unsuccessful; therefore, we searched for other molecules that could oxidize the enzyme. Since the positive density was large, one of the best possible explanations to occupy this density was glutathione (GSH) [35,36]. The molecule was manually modeled with the GSH.CIF file from CCP4.…”

Section: Oxidized Cys149 In the Gapdh Modelmentioning

confidence: 99%

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

2019

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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 express. Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) is a multi-functional protein that has been used as a control marker for basal function and it is known to undergo cysteine oxidation under different types of cellular stress. Here, we report the 3D structure of the endogenous GAPDH purified from stressed E. coli cells expressing a eukaryotic protein. The structure was solved at 1.64 Å using single-wavelength anomalous dispersion (SAD) phasing with a selenium-modified enzyme. Interestingly, each GAPDH monomer contains a molecule of glyceraldehyde-3 phosphate in a non-previously identified site. Furthermore, the catalytic Cys149 is covalently attached to a ~300 Da molecule, possibly glutathione. This modification alters the conformation of an adjacent alpha helix in the catalytic domain, right opposite to the NAD+ binding site. The conformation of the alpha helix is stabilized after soaking the crystals with NAD+. These results exemplify the effects that the overexpression of an exogenous protein has over the host proteins and sheds light on the structural changes that large oxidant molecules on the catalytic cysteine produce for the GAPDH enzyme.

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Influence of Oxidative Stress on Catalytic and Non-glycolytic Functions of Glyceraldehyde-3-phosphate Dehydrogenase

Cited by 27 publications

References 113 publications

Sperm preparedness and adaptation to osmotic and pH stressors relate to functional competence of sperm in Bos taurus

Sperm preparedness and adaptation to osmotic and pH stressors relate to functional competence of sperm in Bos taurus

Glyceraldehyde-3-phosphate Dehydrogenase Is a Multifaceted Therapeutic Target

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

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