Glycation of Aspartate Aminotransferase and Conformational Flexibility

Seidler, Norbert W.; Seibel, Ines

doi:10.1006/bbrc.2000.3626

Cited by 19 publications

(11 citation statements)

References 17 publications

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“…This observation is consistent with other studies involving similar chemical modifications of proteins where conformational flexibility decreases. 12,32 We also observed that acrolein decreased intrinsic protein fluorescence (Fig. 4) suggesting that there may be increased quenching by bound PLP in the modified cAAT due to rigidification of the protein.…”

Section: Discussionmentioning

confidence: 60%

Acrolein Modifies and Inhibits Cytosolic Aspartate Aminotransferase

Southwell

Yeargans

Kowalewski

et al. 2002

Journal of Enzyme Inhibition and Medicinal Chemistry

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Acrolein is a reactive lipid peroxidation byproduct, which is found in ischemic tissue. We examined the effects of acrolein on cytosolic aspartate aminotransferase (cAAT), which is an enzyme that was previously shown to be inhibited by glycating agents. cAAT is thought to protect against ischemic injury. We observed that acrolein cross-linked cAAT subunits as evidenced by the presence of high molecular weight bands following SDS-PAGE. Acrolein-modified cAAT resisted thermal denaturation when compared with native cAAT. We also observed a decrease in intrinsic fluorescence (290 nm, ex; 380 nm, em). These observations are consistent with an acrolein-induced change in conformation that is more rigid and compact than native cAAT, suggesting that intramolecular cross-links occurred. Acrolein also inhibited activity, and the inhibition of enzyme activity correlated with the acrolein-induced formation of cAAT cross-links.

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Section: Discussionmentioning

confidence: 60%

Acrolein Modifies and Inhibits Cytosolic Aspartate Aminotransferase

Southwell

Yeargans

Kowalewski

et al. 2002

Journal of Enzyme Inhibition and Medicinal Chemistry

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“…3b). Increase in the hydrophobicity of BSA after glycation also influenced the thermal stability of glycated BSA [27,28]. However, the change in the Tm of BSA which was glycated in the presence of nicotine was less than that in the absence of nicotine (Fig.…”

Section: Nicotine Protects Glycated Proteins Against Aggregationmentioning

confidence: 96%

Nicotine Reduces the Cytotoxic Effect of Glycated Proteins on Microglial Cells

2009

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Protein glycation has been implicated to play an important role in the pathogenesis of Alzheimer's disease and other neurological disorders. Glycation induces extensive change in the structure of proteins and leads to the formation of cross beta-structures which are detected by the receptor of AGE. Activation of these receptors by glycated proteins transduces the signaling pathways which contribute to neuronal malfunctions and death. Glycated proteins can induce activation of microglia, which exacerbate the pathology of Alzheimer's disease by causing chronic inflammation. Compounds which can decelerate glycation or prevent the structural change of proteins during glycation should be of therapeutic interest. In this study the effect of nicotine on protein glycation and structural alterations of the glycated protein were investigated. Bovine serum albumin, as a model protein, was glycated by glucose in the presence or absence of nicotine and structural changes in the protein together with the effect of glycated proteins on the activation of microglia via receptor of AGE were studied. Nicotine not only could not prevent glycation, but even increased protein glycation. However, proteins glycated in the presence of nicotine did not form beta-structures. In the absence of this secondary structure glycated proteins cannot bind to the receptor of AGE on microglia. Here we showed that glycated proteins prepared in the presence of nicotine could not activate microglial cells.

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“…The trioses are more reactive than the cyclic pentoses or hexoses that have their carbonyl groups masked in a hemiacetal linkage. The reactions of glyceraldehyde or glyceraldehyde 3-phosphate with cellular proteins covalently cross-link proteins intra-and inter-molecularly [22] and decrease their conformational flexibility [23]. A perhaps unrecognized feature of the neurodegenerative diseases (or, so-called conformational diseases) is that the hallmark proteins all lose their ability to exist in conformational substrates.…”

Section: Glycolytic Interactomementioning

confidence: 99%

Multiple Binding Partners

Seidler

2012

GAPDH: Biological Properties and Diversity

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GAPDH interacts with a plethora of diverse cellular proteins. The network of interacting partners, or interactome, is presented for GAPDH with the interacting molecules grouped into specific functional and structural categories. By organizing the binding partners in this way, certain common structural features are beginning to surface, such as acidic dipeptide sequences that are found in several of these binding proteins. Additionally, the consensus sequences for target polynucleotides are being brought to light. The categories, which are presented according to function, offer an opportunity for research into the corresponding structural correlates to these interactions. Recent discoveries of interacting proteins have revealed novel relationships that are generating emerging mechanisms. Proteins that are associated with age-related neurodegenerative diseases appear to be particularly prone to binding GAPDH, suggesting that GAPDH may be playing a role in these diseases. Neurodegenerative diseases that are discussed are the conformational diseases of aging, suggesting that GAPDH may be a global sensor for cellular conformational stress. In addition to GAPDH's oxidoreductase activity, several other enzymatic functions have been discovered, including peroxidase, nitrosylase, mono-ADP-ribosylase and kinase activities.

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Glycation of Aspartate Aminotransferase and Conformational Flexibility

Cited by 19 publications

References 17 publications

Acrolein Modifies and Inhibits Cytosolic Aspartate Aminotransferase

Acrolein Modifies and Inhibits Cytosolic Aspartate Aminotransferase

Nicotine Reduces the Cytotoxic Effect of Glycated Proteins on Microglial Cells

Multiple Binding Partners

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