Glutaminyl cyclases from animals and plants: a case of functionally convergent protein evolution
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Stephan Schilling
Abstract
Several mammalian peptide hormones and proteins from plant and animal origin contain an N-terminal pyroglutamic acid (pGlu) residue. Frequently, the moiety is important in exerting biological function in either mediating interaction with receptors or stabilizing against N-terminal degradation. Glutaminyl cyclases (QCs) were isolated from different plants and animals catalyzing pGlu formation. The recent resolution of the 3D structures of Carica papaya and human QCs clearly supports different evolutionary origins of the proteins, which is also reflected by different enzymatic mechanisms. The broad substrate specificity is revealed by the heterogeneity of physiological substrates of plant and animal QCs, including cytokines, matrix proteins and pathogenesis-related proteins. Moreover, recent evidence also suggests human QC as a catalyst of pGlu formation at the N-terminus of amyloid peptides, which contribute to Alzheimer's disease. Obviously, owing to its biophysical properties, the function of pGlu in plant and animal proteins is very similar in terms of stabilizing or mediating protein and peptide structure. It is possible that the requirement for catalysis of pGlu formation under physiological conditions may have triggered separate evolution of QCs in plants and animals.
©2008 by Walter de Gruyter Berlin New York
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- Editorial
- Farewell to Hans Fritz, Executive Editor
- Guest Editorial
- Highlight on Advances in Proteolysis Research
- Highlight: 5th General Meeting of the International Proteolysis Society 2007
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- Alternative pathways for production of β-amyloid peptides of Alzheimer's disease
- Bauhinia Kunitz-type proteinase inhibitors: structural characteristics and biological properties
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- Intestine-specific expression of green fluorescent protein-tagged cathepsin B: proof-of-principle experiments
- Substrate specificity determination of mouse implantation serine proteinase and human kallikrein-related peptidase 6 by phage display
- In vivo analysis reveals substrate-gating mutants of a rhomboid intramembrane protease display increased activity in living cells
- Human monocytes augment invasiveness and proteolytic activity of inflammatory breast cancer
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- Protein Structure and Function
- Contribution of the C30/C75 disulfide bond to the biological properties of onconase
- Conformational changes in bovine lactoferrin induced by slow or fast temperature increases
Articles in the same Issue
- Editors' Note
- Editors' Note
- Editorial
- Farewell to Hans Fritz, Executive Editor
- Guest Editorial
- Highlight on Advances in Proteolysis Research
- Highlight: 5th General Meeting of the International Proteolysis Society 2007
- Proteinases as hormones: targets and mechanisms for proteolytic signaling
- Glutaminyl cyclases from animals and plants: a case of functionally convergent protein evolution
- Alternative pathways for production of β-amyloid peptides of Alzheimer's disease
- Bauhinia Kunitz-type proteinase inhibitors: structural characteristics and biological properties
- Angiotensin-converting enzyme limits inflammation elicited by Trypanosoma cruzi cysteine proteases: a peripheral mechanism regulating adaptive immunity via the innate kinin pathway
- How Na+ activates thrombin – a review of the functional and structural data
- Cancer cells, adipocytes and matrix metalloproteinase 11: a vicious tumor progression cycle
- Isoaspartate residues dramatically influence substrate recognition and turnover by proteases
- Isoaspartate-containing amyloid precursor protein-derived peptides alter efficacy and specificity of potential β-secretases
- Trial of the cysteine cathepsin inhibitor JPM-OEt on early and advanced mammary cancer stages in the MMTV-PyMT-transgenic mouse model
- Metastasis-associated C4.4A, a GPI-anchored protein cleaved by ADAM10 and ADAM17
- Intestine-specific expression of green fluorescent protein-tagged cathepsin B: proof-of-principle experiments
- Substrate specificity determination of mouse implantation serine proteinase and human kallikrein-related peptidase 6 by phage display
- In vivo analysis reveals substrate-gating mutants of a rhomboid intramembrane protease display increased activity in living cells
- Human monocytes augment invasiveness and proteolytic activity of inflammatory breast cancer
- Regulation of cathepsin K activity by hydrogen peroxide
- Protein Structure and Function
- Contribution of the C30/C75 disulfide bond to the biological properties of onconase
- Conformational changes in bovine lactoferrin induced by slow or fast temperature increases
