endopeptidase k


Summary: An enzyme that catalyzes the hydrolysis of keratin, and of other proteins with subtilisin-like specificity. It hydrolyses peptide amides. Endopeptidase K is from the mold Tritirachium album Limber. (Enzyme Nomenclature, 1992) EC

Top Publications

  1. Pastrana M, Sajnani G, Onisko B, Castilla J, Morales R, Soto C, et al. Isolation and characterization of a proteinase K-sensitive PrPSc fraction. Biochemistry. 2006;45:15710-7 pubmed
    ..PK-sensitive PrPSc isolates should prove useful for structural studies to help understand fundamental issues of the molecular biology of PrPSc and in the quest to design tests to detect preclinical prion disease. ..
  2. Langeveld J, Erkens J, Rammel I, Jacobs J, Davidse A, van Zijderveld F, et al. Four independent molecular prion protein parameters for discriminating new cases of C, L, and h bovine spongiform encephalopathy in cattle. J Clin Microbiol. 2011;49:3026-8 pubmed publisher
    ..One H BSE case, three L BSE cases, six C BSE cases, and one unusual classical BSE (C BSE) case are reported. ..
  3. Thackray A, Hopkins L, Bujdoso R. Proteinase K-sensitive disease-associated ovine prion protein revealed by conformation-dependent immunoassay. Biochem J. 2007;401:475-83 pubmed
    ..Collectively, our results show that the level of PrPSc in brain samples from cases of natural scrapie display genotypic differences and that a significant amount of this material is PK-sensitive. ..
  4. Cali I, Castellani R, Yuan J, Al Shekhlee A, Cohen M, Xiao X, et al. Classification of sporadic Creutzfeldt-Jakob disease revisited. Brain. 2006;129:2266-77 pubmed
    ..These data indicate that the differentiation of sCJDMM1 into two subgroups is not currently justified. ..
  5. Jacobs J, Langeveld J, Biacabe A, Acutis P, Polak M, Gavier Widen D, et al. Molecular discrimination of atypical bovine spongiform encephalopathy strains from a geographical region spanning a wide area in Europe. J Clin Microbiol. 2007;45:1821-9 pubmed
  6. Deleault A, Deleault N, Harris B, Rees J, Supattapone S. The effects of prion protein proteolysis and disaggregation on the strain properties of hamster scrapie. J Gen Virol. 2008;89:2642-50 pubmed publisher
  7. Zou R, Fujioka H, Guo J, Xiao X, Shimoji M, Kong C, et al. Characterization of spontaneously generated prion-like conformers in cultured cells. Aging (Albany NY). 2011;3:968-84 pubmed
    ..Our results indicate that iPrPC may be formed more readily in an intracellular compartment and that a significant increase in PrPT183A aggregation may be attributable to the inhibition of autophagy. ..
  8. Angelini S, Boy D, Schiltz E, Koch H. Membrane binding of the bacterial signal recognition particle receptor involves two distinct binding sites. J Cell Biol. 2006;174:715-24 pubmed
    ..This interaction is stabilized by the N-terminal A-domain of FtsY, which probably serves as a transient lipid anchor. ..
  9. De Franceschi G, Frare E, Bubacco L, Mammi S, Fontana A, de Laureto P. Molecular insights into the interaction between alpha-synuclein and docosahexaenoic acid. J Mol Biol. 2009;394:94-107 pubmed publisher

More Information


  1. Wang F, Wang X, Yuan C, Ma J. Generating a prion with bacterially expressed recombinant prion protein. Science. 2010;327:1132-5 pubmed publisher
    ..Thus, as postulated by the prion hypothesis, the infectivity in mammalian prion disease results from an altered conformation of PrP. ..
  2. Jang A, Lee H, Suk J, Jung J, Kim K, Lee S. Non-classical exocytosis of alpha-synuclein is sensitive to folding states and promoted under stress conditions. J Neurochem. 2010;113:1263-74 pubmed publisher
    ..Together, these results suggest that structurally abnormal, damaged alpha-synuclein proteins translocate preferentially into vesicles and are released from neuronal cells via exocytosis. ..
  3. Corsaro A, Anselmi C, Polano M, Aceto A, Florio T, De Nobili M. The interaction of humic substances with the human prion protein fragment 90-231 affects its protease K resistance and cell internalization. J Biol Regul Homeost Agents. 2010;24:27-39 pubmed
  4. Tao Y, Rao Z, Liu S. Insight derived from molecular dynamics simulation into substrate-induced changes in protein motions of proteinase K. J Biomol Struct Dyn. 2010;28:143-58 pubmed
    ..Our simulation results complement the biochemical and structural studies, highlighting the dynamic mechanism of the functional properties of proteinase K. ..
  5. Dron M, Moudjou M, Chapuis J, Salamat M, Bernard J, Cronier S, et al. Endogenous proteolytic cleavage of disease-associated prion protein to produce C2 fragments is strongly cell- and tissue-dependent. J Biol Chem. 2010;285:10252-64 pubmed publisher
    ..These findings have implications on the molecular analysis of PrP(Sc) and cell pathogenesis of prion infection. ..
  6. Thackray A, Hopkins L, Klein M, Bujdoso R. Mouse-adapted ovine scrapie prion strains are characterized by different conformers of PrPSc. J Virol. 2007;81:12119-27 pubmed
    ..Our data show that mouse-adapted ovine scrapie strains can be discriminated by their distinct conformers of PrPSc, which provides a basis to investigate their diversity at the molecular level. ..
  7. Hagiwara K, Yamakawa Y, Sato Y, Nakamura Y, Tobiume M, Shinagawa M, et al. Accumulation of mono-glycosylated form-rich, plaque-forming PrPSc in the second atypical bovine spongiform encephalopathy case in Japan. Jpn J Infect Dis. 2007;60:305-8 pubmed
  8. Barron R, Campbell S, King D, Bellon A, Chapman K, Williamson R, et al. High titers of transmissible spongiform encephalopathy infectivity associated with extremely low levels of PrPSc in vivo. J Biol Chem. 2007;282:35878-86 pubmed
    ..Reliance on protease-resistant PrP(Sc) as a sole measure of infectivity may therefore in some instances significantly underestimate biological properties of diagnostic samples, thereby undermining efforts to contain and eradicate TSEs. ..
  9. Cronier S, Gros N, Tattum M, Jackson G, Clarke A, Collinge J, et al. Detection and characterization of proteinase K-sensitive disease-related prion protein with thermolysin. Biochem J. 2008;416:297-305 pubmed publisher
    ..Detection of PK-sensitive isoforms of disease-related PrP using thermolysin should be useful for improving diagnostic sensitivity in human prion diseases. ..
  10. Weber P, Giese A, Piening N, Mitteregger G, Thomzig A, Beekes M, et al. Generation of genuine prion infectivity by serial PMCA. Vet Microbiol. 2007;123:346-57 pubmed
  11. Liu S, Meng Z, Fu Y, Zhang K. Insights derived from molecular dynamics simulation into the molecular motions of serine protease proteinase K. J Mol Model. 2010;16:17-28 pubmed publisher
    ..Our simulation study complements the biochemical and structural studies and provides new insights into the dynamic structural basis of the functional properties of this class of enzymes. ..
  12. Bouzalas I, Lörtscher F, Dovas C, Oevermann A, Langeveld J, Papanastassopoulou M, et al. Distinct proteinase K-resistant prion protein fragment in goats with no signs of disease in a classical scrapie outbreak. J Clin Microbiol. 2011;49:2109-15 pubmed publisher
    ..These findings reveal novel aspects of the nature and diversity of the molecular PrP(res) phenotypes in goats and suggest that these animals display a previously unrecognized prion protein disorder. ..
  13. Sajnani G, Pastrana M, Dynin I, Onisko B, Requena J. Scrapie prion protein structural constraints obtained by limited proteolysis and mass spectrometry. J Mol Biol. 2008;382:88-98 pubmed publisher
    ..These results are compatible with a structure consisting of short beta-sheet stretches connected by loops and turns. ..
  14. Wang F, Yang F, Hu Y, Wang X, Wang X, Jin C, et al. Lipid interaction converts prion protein to a PrPSc-like proteinase K-resistant conformation under physiological conditions. Biochemistry. 2007;46:7045-53 pubmed
  15. Owen J, Maddison B, Whitelam G, Gough K. Use of thermolysin in the diagnosis of prion diseases. Mol Biotechnol. 2007;35:161-70 pubmed
    ..In addition, thermolysin provides a complementary tool to proteinase K to allow the study of the contribution of the amino-terminal domain of PrPSc to disease pathogenesis. ..
  16. Boles B, Horswill A. Agr-mediated dispersal of Staphylococcus aureus biofilms. PLoS Pathog. 2008;4:e1000052 pubmed publisher
    ..These findings indicate that induction of the agr system in established S. aureus biofilms detaches cells and demonstrate that the dispersal mechanism requires extracellular protease activity. ..
  17. Seidl K, Goerke C, Wolz C, Mack D, BERGER BACHI B, Bischoff M. Staphylococcus aureus CcpA affects biofilm formation. Infect Immun. 2008;76:2044-50 pubmed publisher
    ..Moreover, we showed that CcpA increased icaA expression and PIA production, presumably over the down-regulation of the tricarboxylic acid cycle genes citB and citZ...
  18. Gretzschel A, Buschmann A, Langeveld J, Groschup M. Immunological characterization of abnormal prion protein from atypical scrapie cases in sheep using a panel of monoclonal antibodies. J Gen Virol. 2006;87:3715-22 pubmed
    ..The 11 kDa band corresponds to a prion protein fragment spanning approximately aa 90-153 and may therefore represent a novel PrP(Sc) type. ..
  19. Liu S, Tao Y, Meng Z, Fu Y, Zhang K. The effect of calciums on molecular motions of proteinase K. J Mol Model. 2011;17:289-300 pubmed publisher
  20. Buschmann A, Gretzschel A, Biacabe A, Schiebel K, Corona C, Hoffmann C, et al. Atypical BSE in Germany--proof of transmissibility and biochemical characterization. Vet Microbiol. 2006;117:103-16 pubmed
    ..These atypical cases suggest the possible existence of sporadic BSE cases in bovines. It is thus feasible that the BSE epidemic in the UK could have also been initiated by an intraspecies transmission from a sporadic BSE case. ..
  21. Klingeborn M, Wik L, Simonsson M, Renstr m L, Ottinger T, Linn T. Characterization of proteinase K-resistant N- and C-terminally truncated PrP in Nor98 atypical scrapie. J Gen Virol. 2006;87:1751-60 pubmed publisher
    ..The structural gene of PrP in three Nor98-affected sheep was analysed, but no mutations were found that could be correlated to the aberrant PK-resistant profile observed...
  22. Yanagida F, Chen Y, Onda T, Shinohara T. Durancin L28-1A, a new bacteriocin from Enterococcus durans L28-1, isolated from soil. Lett Appl Microbiol. 2005;40:430-5 pubmed
    ..durans L28-1 is a new natural enterocin variant. Enterococcus durans L28-1 produced a new bacteriocin. This study reports a novel bacteriocin that is produced by Ent. durans that has potential for use as a food preservative. ..
  23. Jackson G, McKintosh E, Flechsig E, Prodromidou K, Hirsch P, Linehan J, et al. An enzyme-detergent method for effective prion decontamination of surgical steel. J Gen Virol. 2005;86:869-78 pubmed
    ..The prion-degrading reagents identified in this study are readily available, inexpensive, non-corrosive to instruments, non-hazardous to staff and compatible with current equipment and procedures used in hospital sterilization units. ..
  24. Manning M, Colon W. Structural basis of protein kinetic stability: resistance to sodium dodecyl sulfate suggests a central role for rigidity and a bias toward beta-sheet structure. Biochemistry. 2004;43:11248-54 pubmed
    ..Remarkably, most of the kinetically stable SDS-resistant proteins in this study are oligomeric beta-sheet proteins, suggesting a bias of these types of structures toward kinetic stability. ..
  25. Balguerie A, Dos Reis S, Coulary Salin B, Chaignepain S, Sabourin M, Schmitter J, et al. The sequences appended to the amyloid core region of the HET-s prion protein determine higher-order aggregate organization in vivo. J Cell Sci. 2004;117:2599-610 pubmed
  26. Polverino De Laureto P, Taddei N, Frare E, Capanni C, Costantini S, Zurdo J, et al. Protein aggregation and amyloid fibril formation by an SH3 domain probed by limited proteolysis. J Mol Biol. 2003;334:129-41 pubmed
    ..In addition, the disordered and non-native character of the polypeptide chains in the early aggregates could be important in determining the high cytotoxicity that has been revealed in previous studies of these species. ..
  27. Neumann M, Kahle P, Giasson B, Ozmen L, Borroni E, Spooren W, et al. Misfolded proteinase K-resistant hyperphosphorylated alpha-synuclein in aged transgenic mice with locomotor deterioration and in human alpha-synucleinopathies. J Clin Invest. 2002;110:1429-39 pubmed
    ..The transgenic mice showed a progressive deterioration of locomotor function. Thus, misfolding and hyperphosphorylation of alphaS may cause dysfunction of affected brain regions. ..
  28. Corsaro A, Paludi D, Villa V, D Arrigo C, Chiovitti K, Thellung S, et al. Conformation dependent pro-apoptotic activity of the recombinant human prion protein fragment 90-231. Int J Immunopathol Pharmacol. 2006;19:339-56 pubmed
    ..In conclusion, we report that the toxicity of hPrP90-231 is dependent on its three-dimensional structure, as is supposed to occur for the pathogen PrP during TSE. ..
  29. Kreft S, Wang L, Hochstrasser M. Membrane topology of the yeast endoplasmic reticulum-localized ubiquitin ligase Doa10 and comparison with its human ortholog TEB4 (MARCH-VI). J Biol Chem. 2006;281:4646-53 pubmed
    ..Finally, we provide evidence that the likely human Doa10 ortholog, TEB4 (MARCH-VI), adopts a topology similar to that of Doa10...
  30. Yao H, Han J, Gao J, Zhang J, Zhang B, Guo Y, et al. Comparative study of the effects of several chemical and physical treatments on the activity of protease resistance and infectivity of scrapie strain 263K. J Vet Med B Infect Dis Vet Public Health. 2005;52:437-43 pubmed
    ..Our data provide the useful evidences for several commonly used methods to inactivate TSEs agent and suggest that it is inappropriate to use PrPSc as a surrogate for TSEs infectivity in inactivation experiments. ..
  31. Lashuel H, Petre B, Wall J, Simon M, Nowak R, Walz T, et al. Alpha-synuclein, especially the Parkinson's disease-associated mutants, forms pore-like annular and tubular protofibrils. J Mol Biol. 2002;322:1089-102 pubmed
    ..The formation of pore-like oligomeric structures may explain the membrane permeabilization activity of alpha-synuclein protofibrils. These structures may contribute to the pathogenesis of PD. ..
  32. Zou W, Capellari S, Parchi P, Sy M, Gambetti P, Chen S. Identification of novel proteinase K-resistant C-terminal fragments of PrP in Creutzfeldt-Jakob disease. J Biol Chem. 2003;278:40429-36 pubmed
    ..The finding of PrP-CTF12/13 in CJD brains widens the heterogeneity of the PK-resistant PrP fragments associated with prion diseases and may provide useful insights toward the understanding of the PrPSc structure and its formation. ..
  33. Hill A, Joiner S, Beck J, Campbell T, Dickinson A, Poulter M, et al. Distinct glycoform ratios of protease resistant prion protein associated with PRNP point mutations. Brain. 2006;129:676-85 pubmed
    ..These data extend the spectrum of recognized PrP(Sc) types seen in human prion diseases and provide further insight into the generation of diverse clinicopathological phenotypes associated with inherited prion disease. ..
  34. Curin Serbec V, Bresjanac M, Popovic M, Pretnar Hartman K, Galvani V, Rupreht R, et al. Monoclonal antibody against a peptide of human prion protein discriminates between Creutzfeldt-Jacob's disease-affected and normal brain tissue. J Biol Chem. 2004;279:3694-8 pubmed
    ..The PrP(Sc)-specific epitope is disrupted by denaturation. We conclude that the C-terminal part of PrP in disease-associated PrP(Sc) aggregates forms a structural epitope whose conformation is distinct from that of PrP(C). ..
  35. Zaidi S, Richardson S, Capellari S, Song L, Smith M, Ghetti B, et al. Characterization of the F198S prion protein mutation: enhanced glycosylation and defective refolding. J Alzheimers Dis. 2005;7:159-71; discussion 173-80 pubmed
    ..Further, the F198S mutation significantly affects glycosylation of the mutant protein. ..
  36. Bocharova O, Breydo L, Parfenov A, Salnikov V, Baskakov I. In vitro conversion of full-length mammalian prion protein produces amyloid form with physical properties of PrP(Sc). J Mol Biol. 2005;346:645-59 pubmed
  37. Zou W, Zheng J, Gray D, Gambetti P, Chen S. Antibody to DNA detects scrapie but not normal prion protein. Proc Natl Acad Sci U S A. 2004;101:1380-5 pubmed
    ..Our finding that anti-DNA Abs and gene 5 protein specifically target disease-associated DNA-PrP complexes in a wide variety of species and disease phenotypes opens new avenues in the study and diagnosis of prion diseases. ..
  38. Yamakawa Y, Hagiwara K, Nohtomi K, Nakamura Y, Nishijima M, Higuchi Y, et al. Atypical proteinase K-resistant prion protein (PrPres) observed in an apparently healthy 23-month-old Holstein steer. Jpn J Infect Dis. 2003;56:221-2 pubmed
  39. Magalhães A, Baron G, Lee K, Steele Mortimer O, Dorward D, Prado M, et al. Uptake and neuritic transport of scrapie prion protein coincident with infection of neuronal cells. J Neurosci. 2005;25:5207-16 pubmed
    ..These experiments visualize and characterize the initial steps associated with prion infection and transport within neuronal cells. ..
  40. Mesojednik S, Legisa M. Posttranslational modification of 6-phosphofructo-1-kinase in Aspergillus niger. Appl Environ Microbiol. 2005;71:1425-32 pubmed
    ..niger cells, while from the kinetic parameters determined for both isolated forms it could be concluded that the fragmented enzyme might be more efficient under physiological conditions. ..
  41. Buettner K, Hertel T, Pietzsch M. Increased thermostability of microbial transglutaminase by combination of several hot spots evolved by random and saturation mutagenesis. Amino Acids. 2012;42:987-96 pubmed publisher
    ..A triple mutant with amino acid substitutions at sites 2, 289 and 294 exhibits a temperature optimum of 60°C, which is 10°C higher than that of the wild-type enzyme. ..
  42. Yuan F, Yang L, Zhang Z, Wu W, Zhou X, Yin X, et al. Cellular prion protein (PrPC) of the neuron cell transformed to a PK-resistant protein under oxidative stress, comprising main mitochondrial damage in prion diseases. J Mol Neurosci. 2013;51:219-24 pubmed publisher
    ..Our results suggested that neuron cell damage, and particularly mitochondrial damage, was induced by oxidative stress. This damage may be the initial cause of a given prion disease. ..
  43. Chatake T, Ishikawa T, Yanagisawa Y, Yamada T, Tanaka I, Fujiwara S, et al. High-resolution X-ray study of the effects of deuteration on crystal growth and the crystal structure of proteinase K. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2011;67:1334-8 pubmed publisher
    ..Moreover, a positive correlation between the root-mean-squared differences and B factors indicated that no systematic difference existed. ..
  44. Ganeshnarayan K, Velliyagounder K, Furgang D, Fine D. Human salivary cystatin SA exhibits antimicrobial effect against Aggregatibacter actinomycetemcomitans. J Periodontal Res. 2012;47:661-73 pubmed publisher
    ..actinomycetemcomitans, and future studies determining the mechanism of action are necessary. The study also shows the ability of cystatin SA to reduce significantly the binding of A. actinomycetemcomitans to BECs. ..
  45. Blazusiak E, Florczyk D, Jura J, Potempa J, Koziel J. Differential regulation by Toll-like receptor agonists reveals that MCPIP1 is the potent regulator of innate immunity in bacterial and viral infections. J Innate Immun. 2013;5:15-23 pubmed publisher
    ..Taken together, our results implicate MCPIP1 as a potent regulator of innate immunity, which can be strongly engaged in the pathogenesis of acute and chronic infective diseases. ..
  46. Shiraishi N, Inai Y, Hirano Y, Ihara Y. Calreticulin inhibits prion protein PrP-(23-98) aggregation in vitro. Biosci Biotechnol Biochem. 2011;75:1625-7 pubmed
    ..The results indicated that CRT suppressed PrP-(23-98) aggregation, and that CRT-mediated solubilization occurred in the aggregates. ..
  47. Verma R, Ghosh J. Structural and functional changes in a synthetic S5 segment of KvLQT1 channel as a result of a conserved amino acid substitution that occurs in LQT1 syndrome of human. Biochim Biophys Acta. 2010;1798:461-70 pubmed publisher
    ..We speculate that the structural and functional changes related to the glycine to serine amino acid substitution in the S5 segment may also influence the activity of the whole KvLQT1 channel. ..
  48. Götte D, Benestad S, Laude H, Zurbriggen A, Oevermann A, Seuberlich T. Atypical scrapie isolates involve a uniform prion species with a complex molecular signature. PLoS ONE. 2011;6:e27510 pubmed publisher
    ..These findings show similarities to those for other prion diseases in animals and humans, and lay the groundwork for future comparative research. ..
  49. Tang Q, Li D, Xu J, Wang J, Zhao Y, Li Z, et al. Mechanism of inactivation of murine norovirus-1 by high pressure processing. Int J Food Microbiol. 2010;137:186-9 pubmed publisher
    ..The integrity of the capsid was not affect by HPP. Partial motif changes of the viral capsid caused by HPP were accessed by induced sensitivity to proteinase K. ..
  50. Comelli H, Rimstad E, Larsen S, Myrmel M. Detection of norovirus genotype I.3b and II.4 in bioaccumulated blue mussels using different virus recovery methods. Int J Food Microbiol. 2008;127:53-9 pubmed publisher
    ..3b and GII.4 (3.0% and 3.5% recovery respectively). The results show that the processing method influences the possibility to detect different variants of NoV. ..
  51. Li D, Liu J, Chu L, Liu J, Yang Z. A novel mixed-component molecular hydrogel system with excellent stabilities. Chem Commun (Camb). 2012;48:6175-7 pubmed publisher
    ..We report a novel mixed-component molecular hydrogel system with excellent stabilities against dilution and enzyme digestion. ..
  52. Frick J, Schenk K, Quitadamo M, Kahl F, Köberle M, Bohn E, et al. Lactobacillus fermentum attenuates the proinflammatory effect of Yersinia enterocolitica on human epithelial cells. Inflamm Bowel Dis. 2007;13:83-90 pubmed
    ..These data suggest that L. fermentum may have probiotic properties modulating intestinal inflammatory responses and might offer new therapeutic strategies in the treatment of intestinal inflammatory diseases. ..
  53. Montigny C, Picard M, Lenoir G, Gauron C, Toyoshima C, Champeil P. Inhibitors bound to Ca(2+)-free sarcoplasmic reticulum Ca(2+)-ATPase lock its transmembrane region but not necessarily its cytosolic region, revealing the flexibility of the loops connecting transmembrane and cytosolic domains. Biochemistry. 2007;46:15162-74 pubmed
    ..2,5-Di-tert-butyl-1,4-dihydroxybenzene or cyclopiazonic acid, inhibitors which also bind in or near the transmembrane region, also produce similar overall effects on Ca2+-free ATPase. ..