Proteolytic enzymes

About: Proteolytic enzymes is a research topic. Over the lifetime, 23096 publications have been published within this topic receiving 835544 citations.

Protein sequence comparisons show that the ‘pseudoproteases’ encoded by poxviruses and certain retroviruses belong to the deoxyuridine triphosphatase family

Abstract: Amino acid sequence comparisons show extensive similarities among the deoxyuridine triphosphatases (dUTPases) of Escherichia coli and of herpesviruses, and the 'protease-like' or 'pseudoprotease' sequences encoded by certain retroviruses in the oncovirus and lentivirus families and by poxviruses. These relationships suggest strongly that the 'pseudoproteases' actually are dUTPases, and have not arisen by duplication of an oncovirus protease gene as had been suggested. The herpesvirus dUTPase sequences differ from the others in that they are longer (about 370 residues, against around 140) and one conserved element ('Motif 3') is displaced relative to its position in the other sequences; a model involving internal duplication of the herpesvirus gene can account effectively for these observations. Sequences closely similar to Motif 3 are also found in phosphofructokinases, where they form part of the active site and fructose phosphate binding structure; thus these sequences may represent a class of structural element generally involved in phosphate transfer to and from glycosides.

Posttranslational modification of class III beta-tubulin.

Abstract: The charge heterogeneity of class III beta-tubulin (beta III) during neural development was analyzed by high-resolution isoelectric focusing/two-dimensional polyacrylamide gel electrophoresis in combination with site-specific proteolytic digestion and immunological detection. The number of beta III isoforms (charge variants) gradually increases from one in embryonic brain to seven in adult brain. All of the charge heterogeneity is due to posttranslationally modified sites located within the extreme C-terminal region of the beta III polypeptide. One beta III isoform is present in testis, the only other tissue in which this isotype is expressed. The testis beta III isoform cofocuses with the earliest-appearing embryonic brain beta III charge variant. Our results indicate that the posttranslational modifications of beta III are developmentally regulated, occur at more than one site, and are neuron-specific. The location of these modifications within the extreme C-terminal domain suggests that their function is to modulate the interaction of tubulin with microtubule-associated proteins.

Effects of proteolytic enzymes on function and structure of frog neuromuscular junctions

Abstract: 1. Frog cutaneous pectoris nerve-muscle preparations were incubated with collagenase and protease and examined with electrophysiological and electron microscopic techniques. 2. The physiological properties and intracellular ultrastructural appearance of individual muscle and nerve cells were not affected by the enzyme treatment. However, neuromuscular transmission and the morphology of the nerve-muscle junction were altered. 3. Collagenase produced an irreversible loss of activity of end-plate cholinesterase and a partial loss of stainable ‘synaptic cleft material’. 4. Protease produced these changes and, in addition, the entire basement membrane was digested, which led to ‘synaptic disjunction’ of nerve terminals and muscle end-plates.

Elastin as a matrikine

Abstract: The fact that elastin peptides, the degradation products of the extracellular matrix protein elastin, are chemotactic for numerous cell types, promote cell cycle progression and induce release of proteolytic enzymes by stromal and cancer cells, strongly suggests that their presence in tissues could contribute to tumour progression. Thus, elastin peptides qualify as matrikines, i.e. peptides originating from the fragmentation of matrix proteins and presenting biological activities. After a brief description of their origin, the biological activities of these peptides are reviewed, emphasising their potential role in cancer. The nature of their receptor and the signalling events it controls are also discussed. Finally, the structural selectivity of the elastin complex receptor is presented, leading to the concept of elastokine (matrikine originating from elastin fragmentation) and morpho-elastokine, i.e. peptides presenting a conformation similar to that of bioactive elastin peptides and mimicking their effects.

Arteriogenesis, a new concept of vascular adaptation in occlusive disease

Abstract: The formation of collateral arteries as a process adaptive to arterial occlusion is now called 'arteriogenesis' to emphasize the difference to angiogenesis, the formation of capillaries by sprouting from pre-existent ones (W Schaper, I Buschmann Cardiovasc Res 1999; 43: 835-7; I Buschmann, W Schaper J Pathol 2000; 190: 338-42; D Scholz et al Virchows Arch 2000; 436: 257-70) The differences are that collaterals develop from pre-existing arterioles and that circulating monocytes adhere to endothelium that had been activated by the high shear stress generated by the large pressure differences between perfusion territories Monocytes are the major producers of growth factors and of proteolytic enzymes that enable smooth muscle cells to migrate and divide The nature of the growth factors remains uncertain Neither FGF-1/2 nor VEGF is expressed on the transcriptional or translational level in collaterals proper and in the tissue surrounding them Only FGF receptor 1 has a brief window of upregulation shortly after arterial occlusion While transgenic overexpression of FGF-1 increases number and branching of arterioles, targeted disruption of FGF-1/2 does not negatively influence arteriogenesis Cytokines that attract monocytes or prolong the life span of monocytes (MCP-1, GM CSF) are strong arteriogenic factors Collateral vessels exhibit the same morphology whether they had formed in the heart, limbs or brain or in dogs, rabbits or mouse They are tortuous because they also increase lengthwise in a restricted space In animals larger than the mouse, they develop an intima, and initially, many arterioles participate in arteriogenesis, but only a few mature into large arterial channels which, when arterial occlusion had proceeded slowly enough, can replace the occluded artery to a significant proportion Therapy with a single growth factor in animals with occluded femoral arteries significantly increases the speed of arteriogenesis but does not significantly increase the level of adaptation It appears that the mastergene for arteriogenesis still awaits discovery