An analysis of substrate binding interactions in the heme peroxidase enzymes: A structural perspective

In 2008 melamine-contaminated infant formula and dairy products in China led to over 50,000 hospitalizations of children due to renal injuries. In North America during 2007 and in Asia during 2004, melamine-contaminated pet food products resulted in numerous pet deaths due to renal failure. Animal studies have confirmed the potent renal toxicity of melamine combined with cyanuric acid. We showed previously that the solubility of melamine cyanurate is low at physiologic pH and ionic strength, provoking us to speculate how toxic levels of these compounds could be transported through the circulation without crystallizing until passing into the renal filtrate. We hypothesized that melamine might be sequestered by heme proteins, which could interfere with heme enzyme activity. Four heme peroxidase enzymes were selected for study: horseradish peroxidase (HRP), lactoperoxidase (LPO), and cyclooxygenase-1 and -2 (COX-1 and -2). Melamine exhibited noncompetitive inhibition of HRP , and LPO showed a mixed model of inhibition . The inhibition of HRP and LPO was confirmed using a chemiluminescent peroxidase assay. Melamine also exhibited COX-1 inhibition, but inhibition of COX-2 was not detected. Thus, our results demonstrate that melamine inhibits the activity of three heme peroxidases.

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Differences in Gluco and Galacto Substrate-Binding Interactions in a Dual 6Pβ-Glucosidase/6Pβ-Galactosidase Glycoside Hydrolase 1 Enzyme from Bacillus licheniformis

Journal of Chemical Information and Modeling ◽

10.1021/acs.jcim.1c00413 ◽

2021 ◽

Author(s):

Wayde Veldman ◽

Marcelo Vizona Liberato ◽

Valquiria P. Souza ◽

Vitor M. Almeida ◽

Sandro R. Marana ◽

...

Keyword(s):

Bacillus Licheniformis ◽

Glycoside Hydrolase ◽

Substrate Binding ◽

Binding Interactions

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Fibronexus-Like Adhesion Sites are Present at the Invasive Zones of Human Epidermoid Carcinomas

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100053280 ◽

1982 ◽

Vol 40 ◽

pp. 106-109

Author(s):

Irwin I. Singer

Keyword(s):

Cell Cycle ◽

Serum Concentration ◽

Substrate Binding ◽

High Serum ◽

Adhesion Sites ◽

Substrate Adhesion ◽

Focal Contacts ◽

Adhesion Complex ◽

Low Serum

Our previous results indicate that two types of fibronectin-cytoskeletal associations may be formed at the fibroblast surface: dorsal matrixbinding fibronexuses generated in high serum (5% FBS) cultures, and ventral substrate-adhering units formed in low serum (0.3% FBS) cultures. The substrate-adhering fibronexus consists of at least vinculin (VN) and actin in its cytoplasmic leg, and fibronectin (FN) as one of its major extracellular components. This substrate-adhesion complex is localized in focal contacts, the sites of closest substratum approach visualized with interference reflection microscopy, which appear to be the major points of cell-tosubstrate adhesion. In fibroblasts, the latter substrate-binding complex is characteristic of cultures that are arrested at the G1 phase of the cell cycle due to the low serum concentration in their medium. These arrested fibroblasts are very well spread, flattened, and immobile.

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