Families and clans of cysteine peptidases
ABSTRACT The known cysteine peptidases have been classified into 35 sequence families. We argue that these have arisen from at least five separate evolutionary origins, each of which is represented by a set of one or more modern-day families, termed a clan. Clan CA is the largest, containing the papain family, C1, and others with the Cys/His catalytic dyad. Clan CB (His/Cys dyad) contains enzymes from RNA viruses that are distantly related to chymotrypsin. The peptidases of clan CC are also from RNA viruses, but have papain-like Cys/His catalytic sites. Clans CD and CE contain only one family each, those of interleukin-1-converting enzyme and adenovirus L3 proteinase, respectively. A few families cannot yet be assigned to clans. In view of the number of separate origins of enzymes of this type, one should be cautious in generalising about the catalytic mechanisms and other properties of cysteine peptidases as a whole. In contrast, it may be safer to generalise for enzymes within a single family or clan.
- Studies in Surface Science and Catalysis - STUD SURF SCI CATAL. 01/1997; 105:997-1004.
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ABSTRACT: Proteolytic degradation of barley proteins is examined in green (unkilned) malt and germinating seeds from Hordeum vulgare L. cv. Harrington. Zymographic analysis of the Harrington green malt extracts using commercial preparations of barley beta-amylase incorporated as a proteolytic substrate in 2-D SDS gels shows multiple proteolytic activities. A developmental study shows that the several green malt beta-amylase-degrading activities appear at around day 2 of germination. The several activities appear to increase and decrease through 7 days of germination in a coordinated fashion. Gels treated with class-specific proteinase inhibitors show that serine-class proteinase activities are responsible for barley beta-amylase degradation seen on the zymograms. Western blot analysis also shows that proteolytic enzymes recovered from 1-D electrophoretic gels degrade barley beta-amylase, and that the degradation is inhibited by PMSF. This is the first demonstration that malt proteinases are capable of degrading important metabolic enzymes in germinating barley, and the first postulated physiological role for the serine class proteinases in barley malt.Journal of Cereal Science 05/2008; · 1.94 Impact Factor
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ABSTRACT: Hereditäre Amyloidosen stellen eine klinisch und genetisch heterogene Gruppe autosomal-dominant vererbter Krankheiten dar, die durch eine systemische Ablagerung fibrillär aggregierter Proteine charakterisiert sind. Bausteine dieser unlöslichen Proteinablagerungen sind physiologische Eiweiße, die durch genetisch bedingte Konformationsänderungen vermehrt β-Faltblatt-Strukturen ausbilden und dadurch amyloidogen geworden sind. Zumeist handelt es sich dabei um variantes Transthyretin (TTR), von dem heute über 80 Mutationen bekannt sind. In typischen Fällen führen TTR-Amyloidosen zu Polyneuropathien mit deutlicher Beteiligung des autonomen Nervensystems, beidseitigen Karpaltunnelsyndromen, Kardiomyopathie und gastrointestinaler Dysfunktion. Glaskörpertrübungen und Niereninsuffizienz können hinzutreten. Selten dominieren meningovaskuläre Verläufe. Im Einzelfall ist die klinische Manifestation sehr variabel; asymptomatische Genträger kommen vor. Die Erstmanifestation variiert vom frühen Erwachsenenalter bis zum Senium. Die orthotope Lebertransplantation stellt bisher die einzige effektive Therapie dar, die durch Entfernung des Hauptsyntheseorts des amyloidogenen Proteins die ansonsten rasche Progression der Erkrankung stoppt. Therapiemöglichkeiten auf medikamentöser Basis mit dem Ziel, das physiologische TTR zu stabilisieren oder β-Faltblatt-Strukturen zu destabilisieren, werden derzeit intensiv untersucht. Hereditary amyloidoses form a clinically and genetically heterogeneous group of autosomal-dominantly inherited diseases characterized by the ubiquitous extracellular deposit of fibrillary aggregated proteins. Main components of these unsolvable deposits are physiologic proteins that became amyloidogenic through genetically determined conformation changes resulting in an increase in β-sheet structures. In the vast majority of cases, the offending protein is variant transthyretin (TTR), of which over 80 mutations are known. Among these, substitution of valine by methionine in position 30 (TTR-Met30) is the most commonly encountered. In typical cases, TTR amyloidoses present with polyneuropathy, carpal tunnel syndrome, autonomic insufficiency, cardiomyopathy, and gastrointestinal features, occasionally accompanied by vitreous opacities and renal insufficiency. Rarely, involvement of the leptomeningeal or meningovascular structures dominates the clinical picture. The clinical expression is highly variable, with many atypical manifestations. Asymptomatic mutations have recently been identified. The age of onset varies greatly between early adulthood and old age. Late-onset atypical manifestations and occurrence of asymptomatic carriers render identification of affected family members difficult despite autosomal-dominant inheritance. Orthotopic liver transplantation (OLT) is the only effective therapy available today. This OLT stops progression of the disease, which is otherwise invariably fatal, by removal of the main production site of the amyloidogenic protein. However, cardiac involvement may progress after OLT for unknown reasons. The indication for OLT and its success depend on the grade of cardiovascular and autonomic dysfunction at the time of surgery, age, comorbidity, and type of mutation. Alternative treatment modalities with drugs stabilizing the native tetrameric conformation of TTR, inhibiting fibril formation or breaking β-sheet structures, are currently being intensively studied.Der Nervenarzt 01/2002; 73(10):930-936. · 0.86 Impact Factor