Biochimica et biophysica acta
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Biochim. Biophys. Acta · Jul 2013
ReviewMechanisms of conotoxin inhibition of N-type (Ca(v)2.2) calcium channels.
N-type (Ca(v)2.2) voltage-gated calcium channels (VGCC) transduce electrical activity into other cellular functions, regulate calcium homeostasis and play a major role in processing pain information. Although the distribution and function of these channels vary widely among different classes of neurons, they are predominantly expressed in nerve terminals, where they control neurotransmitter release. To date, genetic and pharmacological studies have identified that high-threshold, N-type VGCCs are important for pain sensation in disease models. ⋯ Surprisingly, however, α-conotoxins Vc1.1 and RgIA, also potently inhibit N-type VGCC currents in the sensory DRG neurons of rodents and α9 nAChR knockout mice, via intracellular signaling mediated by G protein-coupled GABAB receptors. Understanding how conotoxins inhibit VGCCs is critical for developing these peptides into analgesics and may result in better pain management. This article is part of a Special Issue entitled: Calcium channels.
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Biochim. Biophys. Acta · Jan 2013
ReviewEfficient, crosswise catalytic promiscuity among enzymes that catalyze phosphoryl transfer.
The observation that one enzyme can accelerate several chemically distinct reactions was at one time surprising because the enormous efficiency of catalysis was often seen as inextricably linked to specialization for one reaction. Originally underreported, and considered a quirk rather than a fundamental property, enzyme promiscuity is now understood to be important as a springboard for adaptive evolution. ⋯ We review the evidence for widespread crosswise promiscuity amongst enzymes that catalyze phosphoryl transfer, including several members of the alkaline phosphatase superfamily, where large rate accelerations between 10(6) and 10(17) are observed for both native and multiple promiscuous reactions. This article is part of a Special Issue entitled: Chemistry and mechanism of phosphatases, diesterases and triesterases.
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Kidney damage induces the expression of a myriad of proteins in the serum and in the urine. The function of these proteins in the sequence of damage and repair is now being studied in genetic models and by novel imaging techniques. One of the most intensely expressed proteins is lipocalin2, also called NGAL or Siderocalin. ⋯ Structure-function studies, imaging studies and clinical studies have revealed that NGAL-Siderocalin is an endogenous antimicrobial with iron scavenging activity. This review discusses the "iron problem" of kidney damage, the tight linkage between kidney damage and NGAL-Siderocalin expression and the potential roles that NGAL-Siderocalin may serve in the defense of the urogenital system. This article is part of a Special Issue entitled: Cell Biology of Metals.
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Biochim. Biophys. Acta · Sep 2012
ReviewAlternative glycosylation modulates function of IgG and other proteins - implications on evolution and disease.
Nearly all membrane and secreted proteins, as well as numerous intracellular proteins are glycosylated. However, contrary to proteins which are defined by their individual genetic templates, glycans are encoded in a complex dynamic network of hundreds of genes which participate in the complex biosynthetic pathway of protein glycosylation. ⋯ The change in the structure of a protein requires mutations in DNA and subsequent selection in the next generation, while even slight alterations in activity or intracellular localization of one or more biosynthetic enzymes are sufficient for the creation of novel glycan structures, which can then perform new functions. Glycome composition varies significantly between individuals, which makes them slightly or even significantly different in their ability to execute specific molecular pathways with numerous implications for development and progression of various diseases. This article is part of a Special Issue entitled Glycoproteomics.
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Non-invasive biomarkers, such as those from serum, are ideal for disease prognosis, staging and monitoring. In the past decade, our understanding of the importance of glycosylation changes with disease has evolved. ⋯ The ability to distinguish differences in the glycosylation of proteins between cancer and control patients emphasizes glycobiology as a promising field for potential biomarker identification. Furthermore, the high-throughput and reproducible nature of the chromatography platform have highlighted extensive applications in biomarker discovery and allowed integration of glycomics with other -omics fields, such as proteomics and genomics, making systems glycobiology a reality. This article is part of a Special Issue entitled Glycoproteomics.