microbial collagenase


Summary: A metalloproteinase which degrades helical regions of native collagen to small fragments. Preferred cleavage is -Gly in the sequence -Pro-Xaa-Gly-Pro-. Six forms (or 2 classes) have been isolated from Clostridium histolyticum that are immunologically cross-reactive but possess different sequences and different specificities. Other variants have been isolated from Bacillus cereus, Empedobacter collagenolyticum, Pseudomonas marinoglutinosa, and species of Vibrio and Streptomyces. EC

Top Publications

  1. Badalamente M, Hurst L. Enzyme injection as nonsurgical treatment of Dupuytren's disease. J Hand Surg Am. 2000;25:629-36 pubmed
    ..Pending further placebo, double-blind studies, collagenase injection to treat Dupuytren's disease may be a safe and effective alternative to surgical fasciectomy. ..
  2. Desai S, Hentz V. Collagenase clostridium histolyticum for Dupuytren's contracture. Expert Opin Biol Ther. 2010;10:1395-404 pubmed publisher
    ..However, with the introduction of collagenase clostridium histolyticum to treat Dupuytren's contractures, physicians and surgeons may be provided with a new, office-based, non-surgical option to treat this disease...
  3. Desai S, Hentz V. The treatment of Dupuytren disease. J Hand Surg Am. 2011;36:936-42 pubmed publisher
    ..This article presents a comprehensive review of the surgical and nonsurgical treatments of Dupuytren disease, with a focus on collagenase...
  4. Hurst L, Badalamente M, Hentz V, Hotchkiss R, Kaplan F, Meals R, et al. Injectable collagenase clostridium histolyticum for Dupuytren's contracture. N Engl J Med. 2009;361:968-79 pubmed publisher
    ..Injection of collagenase clostridium histolyticum, an office-based, nonsurgical option, may reduce joint contractures caused by Dupuytren's disease...
  5. Wilson J, Matsushita O, Okabe A, Sakon J. A bacterial collagen-binding domain with novel calcium-binding motif controls domain orientation. EMBO J. 2003;22:1743-52 pubmed
    ..Furthermore, extensive mutagenesis of conserved surface residues and collagen-binding studies allow us to identify the collagen-binding surface of the protein and propose likely collagen-protein binding models. ..
  6. Shi L, Carson D. Collagenase Santyl ointment: a selective agent for wound debridement. J Wound Ostomy Continence Nurs. 2009;36:S12-6 pubmed publisher
    ..Evidence presented demonstrates that collagenase ointment is an effective, selective, and safe wound debriding agent...
  7. Badalamente M, Hurst L, Hentz V. Collagen as a clinical target: nonoperative treatment of Dupuytren's disease. J Hand Surg Am. 2002;27:788-98 pubmed
    ..The findings of our study may lead to simpler and less invasive nonoperative treatments of joint limitation in which collagen plays a major pathologic role. ..
  8. Gilpin D, Coleman S, Hall S, Houston A, Karrasch J, Jones N. Injectable collagenase Clostridium histolyticum: a new nonsurgical treatment for Dupuytren's disease. J Hand Surg Am. 2010;35:2027-38.e1 pubmed publisher
    ..The Collagenase Option for the Reduction of Dupuytren's (CORD) II study investigated the efficacy and safety of injectable Xiaflex (collagenase clostridium histolyticum), in patients with Dupuytren's contracture...
  9. Shih B, Bayat A. Scientific understanding and clinical management of Dupuytren disease. Nat Rev Rheumatol. 2010;6:715-26 pubmed publisher
    ..Nonsurgical correction of DD contractures can be achieved by Clostridium histolyticum collagenase injection, although the long-term safety and recurrence rate of this procedure requires further assessment. ..

More Information


  1. Shi L, Ermis R, Garcia A, Telgenhoff D, Aust D. Degradation of human collagen isoforms by Clostridium collagenase and the effects of degradation products on cell migration. Int Wound J. 2010;7:87-95 pubmed publisher
  2. Windsor L, Birkedal Hansen H, Birkedal Hansen B, Engler J. An internal cysteine plays a role in the maintenance of the latency of human fibroblast collagenase. Biochemistry. 1991;30:641-7 pubmed
  3. Gelbard M, Lipshultz L, Tursi J, Smith T, Kaufman G, Levine L. Phase 2b study of the clinical efficacy and safety of collagenase Clostridium histolyticum in patients with Peyronie disease. J Urol. 2012;187:2268-74 pubmed publisher
    ..In this phase 2b, double-blind, randomized, placebo controlled study we determined the safety and efficacy of collagenase C. histolyticum and assessed a patient reported outcome questionnaire...
  4. Kaplan F. Collagenase clostridium histolyticum injection for the treatment of Dupuytren's contracture. Drugs Today (Barc). 2011;47:653-67 pubmed publisher
    ..This first-in-class biologic, injectable clostridial collagenase histolyticum, provides a safe, effective alternative to surgery for patients with Dupuytren's contracture...
  5. Haffner J, Fecteau K, Eiler H. Inhibition of collagenase breakdown of equine corneas by tetanus antitoxin, equine serum and acetylcysteine. Vet Ophthalmol. 2003;6:67-72 pubmed
    ..This experiment indicates that tetanus antitoxin, serum and acetylcysteine equally protected corneas from collagenase digestion, in vitro. However, a clinical trial is needed to establish relative therapeutic value. ..
  6. Enghild J, Salvesen G, Brew K, Nagase H. Interaction of human rheumatoid synovial collagenase (matrix metalloproteinase 1) and stromelysin (matrix metalloproteinase 3) with human alpha 2-macroglobulin and chicken ovostatin. Binding kinetics and identification of matrix metalloproteinase cle. J Biol Chem. 1989;264:8779-85 pubmed
    ..These results suggest that alpha 2M may play an important role in regulating the activities of matrix metalloproteinases in the extracellular space. ..
  7. Balamurugan A, Breite A, Anazawa T, Loganathan G, Wilhelm J, Papas K, et al. Successful human islet isolation and transplantation indicating the importance of class 1 collagenase and collagen degradation activity assay. Transplantation. 2010;89:954-61 pubmed publisher
    ..Here, we show the differences between the C1 collagenase found in purified collagenase products manufactured by three suppliers and the impact of differences in C1 between two suppliers on human islet yield...
  8. Boogaard P, Mulder G, Nagelkerke J. Isolated proximal tubular cells from rat kidney as an in vitro model for studies on nephrotoxicity. I. An improved method for preparation of proximal tubular cells and their functional characterization by alpha-methylglucose uptake. Toxicol Appl Pharmacol. 1989;101:135-43 pubmed
    ..4 +/- 0.5 mM and 4.1 +/- 0.9 nmol/min.mg protein, respectively. This transport could almost be completely inhibited by phloridzin, indicating that the uptake is mediated by the brush border glucose carrier. ..
  9. Flagothier C, Pierard G, Quatresooz P. Cutaneous myospherulosis and membranous lipodystrophy: extensive presentation in a patient with severe steroid-induced dermal atrophy. J Eur Acad Dermatol Venereol. 2006;20:457-60 pubmed
    ..We present a case of cutaneous myospherulosis associated with membranous lipodystrophy. The lesions were supervening on severe steroid-induced skin atrophy upon which ointments had been applied. ..
  10. George H, Marchand P, Murphy K, Wiswall B, Dowling R, Giannaras J, et al. Recombinant human 92-kDa type IV collagenase/gelatinase from baculovirus-infected insect cells: expression, purification, and characterization. Protein Expr Purif. 1997;10:154-61 pubmed
    ..The recombinant enzyme provides a useful source of protein for a variety of biochemical and biophysical studies aimed at elucidating the structure and function of human MMP9. ..
  11. Butkowski R, Langeveld J, Wieslander J, Hamilton J, Hudson B. Localization of the Goodpasture epitope to a novel chain of basement membrane collagen. J Biol Chem. 1987;262:7874-7 pubmed
    ..Alternatively, they could represent new molecular species of basement membrane collagen containing a globular domain, comprising M2* and M3, with physicochemical properties very similar to those of collagen IV...
  12. Gelbard M, Goldstein I, Hellstrom W, McMahon C, Smith T, Tursi J, et al. Clinical efficacy, safety and tolerability of collagenase clostridium histolyticum for the treatment of peyronie disease in 2 large double-blind, randomized, placebo controlled phase 3 studies. J Urol. 2013;190:199-207 pubmed publisher
  13. Azzam H, Thompson E. Collagen-induced activation of the M(r) 72,000 type IV collagenase in normal and malignant human fibroblastoid cells. Cancer Res. 1992;52:4540-4 pubmed
    ..The interstitial matrix may thus play an important role in regulating matrix degradation in vivo. ..
  14. Fridman R, Fuerst T, Bird R, Hoyhtya M, Oelkuct M, Kraus S, et al. Domain structure of human 72-kDa gelatinase/type IV collagenase. Characterization of proteolytic activity and identification of the tissue inhibitor of metalloproteinase-2 (TIMP-2) binding regions. J Biol Chem. 1992;267:15398-405 pubmed
    ..These data suggest that both the active site and the COOH-terminal tail of the 72-kDa gelatinase independently and cooperatively participate in TIMP-2 binding. ..
  15. O Gorman D, Kin T, Imes S, Pawlick R, Senior P, Shapiro A. Comparison of human islet isolation outcomes using a new mammalian tissue-free enzyme versus collagenase NB-1. Transplantation. 2010;90:255-9 pubmed publisher
    ..We report our experience using the MTF enzyme in clinical islet isolations compared with Serva NB-1 with modified enzyme delivery method...
  16. Quantin B, Murphy G, Breathnach R. Pump-1 cDNA codes for a protein with characteristics similar to those of classical collagenase family members. Biochemistry. 1989;28:5327-34 pubmed
    ..On the basis of this observation, its size, and its substrate specificity, we suggest that pump-1 might correspond to a previously described uterine metalloproteinase, matrix metalloproteinase 7. ..
  17. Birkedal Hansen B, Moore W, Taylor R, Bhown A, Birkedal Hansen H. Monoclonal antibodies to human fibroblast procollagenase. Inhibition of enzymatic activity, affinity purification of the enzyme, and evidence for clustering of epitopes in the NH2-terminal end of the activated enzyme. Biochemistry. 1988;27:6751-8 pubmed
    ..The inhibitory Mab VI-3 was used for immunoaffinity purification of procollagenase from culture media with a recovery better than 80% and a yield of approximately 1.4 mg of enzyme/L of medium. ..
  18. Mitchell T, Coon C, Brinckerhoff C. Serum amyloid A (SAA3) produced by rabbit synovial fibroblasts treated with phorbol esters or interleukin 1 induces synthesis of collagenase and is neutralized with specific antiserum. J Clin Invest. 1991;87:1177-85 pubmed
  19. Morgan P, Jacobs H, Segrest J, Cunningham L. A comparative study of glycopeptides derived from selected vertebrate collagens. A possible role of the carbohydrate in fibril formation. J Biol Chem. 1970;245:5042-8 pubmed
  20. Welgus H, Jeffrey J, Eisen A. The collagen substrate specificity of human skin fibroblast collagenase. J Biol Chem. 1981;256:9511-5 pubmed
  21. Doi T, Minami T, Itoh M, Aburatani H, Kawabe Y, Kodama T, et al. An alternative form of nucleolysin binds to a T-cluster DNA in the silencer element of platelet factor 4 gene. Biochem Biophys Res Commun. 1997;235:625-30 pubmed
    ..These results indicate that TCBP may participate in the regulation of PF4 gene expression by binding to the T-cluster and the T-rich sequence. ..
  22. Miller E, Harris E, Chung E, Finch J, McCroskery P, Butler W. Cleavage of Type II and III collagens with mammalian collagenase: site of cleavage and primary structure at the NH2-terminal portion of the smaller fragment released from both collagens. Biochemistry. 1976;15:787-92 pubmed
    ..We suggest, then, that a minimum of five residues in collagen alpha chains COOH-terminal to the cleavage site comprise the substrate recognition site. ..
  23. Toyoshima T, Matsushita O, Minami J, Nishi N, Okabe A, Itano T. Collagen-binding domain of a Clostridium histolyticum collagenase exhibits a broad substrate spectrum both in vitro and in vivo. Connect Tissue Res. 2001;42:281-90 pubmed
    ..Therapeutic agents fused with CBD will bind not only to subcutaneous tissues, but also to other tissues containing non-type I collagen. ..
  24. Dreise M, Stenekes M, Werker P. Collagenase Treatment for Dupuytren Disease of the Thumb and First Web. J Hand Surg Am. 2016;41:348-53.e1 pubmed publisher
    ..Collagenase Clostridium histolyticum is a good treatment option for pretendinous cords in thumbs affected with Dupuytren disease because it provides good results, is minimally invasive, and has minor adverse events. Therapeutic IV. ..
  25. Balian G, Click E, Bornstein P. Structure of rat skin collagen 1-CB8. Amino acid sequence of the hydroxylamine-produced fragment HA1. Biochemistry. 1971;10:4470-8 pubmed
  26. Huhtala P, Chow L, Tryggvason K. Structure of the human type IV collagenase gene. J Biol Chem. 1990;265:11077-82 pubmed
    ..There is no CAAT box, but a potential binding site (CCCCAGGC) for the transcription factor AP-2 is located in the first exon. ..
  27. Piening C, Riederer Henderson M. Neutral metalloprotease from tendons. J Orthop Res. 1989;7:228-34 pubmed
  28. Furthmayr H, Wiedemann H, Timpl R, Odermatt E, Engel J. Electron-microscopical approach to a structural model of intima collagen. Biochem J. 1983;211:303-11 pubmed
    ..The unique structure of intima collagen suggests that it originates from a microfibrillar component and that it can be considered a unique collagenous protein, for which we propose the designation type VI collagen. ..
  29. Sarig O, Hass A, Weizenbluth M, Oron A. [Dupuytren's disease]. Harefuah. 2014;153:19-21, 65 pubmed
  30. Sanjuan Cerveró R, Franco Ferrando N, Poquet Jornet J. Use of resources and costs associated with the treatment of Dupuytren's contracture at an orthopedics and traumatology surgery department in Denia (Spain): collagenase clostridium hystolyticum versus subtotal fasciectomy. BMC Musculoskelet Disord. 2013;14:293 pubmed publisher
    ..Long term evolution of CCH treatment is uncertain and the recurrence rate unknown. ..
  31. Foissac R, Camuzard O, Dumas P, Dumontier C, Chignon Sicard B. [Treatment of Dupuytren's contracture by collagenase injection]. Chir Main. 2013;32:199-205 pubmed publisher
    ..Diffusion of this technique is still limited by: the assessment of its cost compared to that of other methods of treatment and particularly the needle fasciotomy, and the evaluation of results over the long-term. ..
  32. Goldberg G, Marmer B, Grant G, Eisen A, Wilhelm S, He C. Human 72-kilodalton type IV collagenase forms a complex with a tissue inhibitor of metalloproteases designated TIMP-2. Proc Natl Acad Sci U S A. 1989;86:8207-11 pubmed
    ..Both activity and activation of the complex can be completely inhibited by further addition of stoichiometric quantities of purified TIMP-2 or recombinant TIMP. ..
  33. Summers T, Irwin M, Mayne R, Balian G. Monoclonal antibodies to type X collagen. Biosynthetic studies using an antibody to the amino-terminal domain. J Biol Chem. 1988;263:581-7 pubmed
    ..In summary, the pulse-chase results and the immune precipitation with monoclonal antibody 6F6 did not detect biosynthetic precursors larger than 59 kDa or proteolytically processed forms of type X. ..
  34. Bruns R. Beaded filaments and long-spacing fibrils: relation to type VI collagen. J Ultrastruct Res. 1984;89:136-45 pubmed
    ..Comparison of the beaded filament structure with molecular models for various collagens described in the literature suggests that they are a filamentous form of type VI collagen. ..
  35. Ivanko O, Varbanets L. [Purification and physico-chemical properties of Streptomyces sp. 1349 collagenase and Streptomyces sp. 1382 keratinase]. Mikrobiol Z. 2004;66:11-24 pubmed
    ..It is shown that the charged aminoacid residues (about 85%) prevail in enzyme molecules. The enzymes are distinguished by pH- and thermooptima. ..
  36. Hansen W, Christie M, Kahn R, Norgaard A, Abel I, Petersen A, et al. Supravital dithizone staining in the isolation of human and rat pancreatic islets. Diabetes Res. 1989;10:53-7 pubmed
  37. Oka S, Itoh N, Kawasaki T, Yamashina I. Primary structure of rat liver mannan-binding protein deduced from its cDNA sequence. J Biochem. 1987;101:135-44 pubmed
    ..Computer analysis of several lectins for sequence homology suggested that the COOH-terminal quarter of the MBP is associated with the calcium binding as well as carbohydrate recognition. ..
  38. Yau W, Dorsett J, Parr E. Characterization of acetylcholine release from enzyme-dissociated myenteric ganglia. Am J Physiol. 1989;256:G233-9 pubmed
  39. Huhtala P, Eddy R, Fan Y, Byers M, Shows T, Tryggvason K. Completion of the primary structure of the human type IV collagenase preproenzyme and assignment of the gene (CLG4) to the q21 region of chromosome 16. Genomics. 1990;6:554-9 pubmed
    ..The gene (CLG4) was localized to 16q21 using somatic cell hybrids and in situ hybridization. ..
  40. Angel P, Baumann I, Stein B, Delius H, Rahmsdorf H, Herrlich P. 12-O-tetradecanoyl-phorbol-13-acetate induction of the human collagenase gene is mediated by an inducible enhancer element located in the 5'-flanking region. Mol Cell Biol. 1987;7:2256-66 pubmed
    ..Differences in enhancer efficiency in different cell lines are interpreted to indicate differences in the activity of a trans-acting factor. ..
  41. Matsushita H, Hijioka M, Hisatsune A, Isohama Y, Shudo K, Katsuki H. Natural and synthetic retinoids afford therapeutic effects on intracerebral hemorrhage in mice. Eur J Pharmacol. 2012;683:125-31 pubmed publisher
    ..ATRA and Am80 also significantly attenuated damage of axon tracts as revealed by amyloid precursor protein immunohistochemistry. These results underscore potential therapeutic values of NR1B agonists for intracerebral hemorrhage. ..
  42. Ito A, Nagase H. Evidence that human rheumatoid synovial matrix metalloproteinase 3 is an endogenous activator of procollagenase. Arch Biochem Biophys. 1988;267:211-6 pubmed
    ..We propose that MMP-3 plays an important role in connective tissue destruction through the activation of procollagenase in addition to its direct action on components of the extracellular matrix. ..
  43. Desrochers P, Jeffrey J, Weiss S. Interstitial collagenase (matrix metalloproteinase-1) expresses serpinase activity. J Clin Invest. 1991;87:2258-65 pubmed
    ..Together, these data indicate that matrix metalloproteinase-1 displays an expanded substrate repertoire that supports the existence of a new interface between connective tissue turnover and Serpin function. ..
  44. Herrmann J, Turck C, Atchison R, Huflejt M, Poulter L, Gitt M, et al. Primary structure of the soluble lactose binding lectin L-29 from rat and dog and interaction of its non-collagenous proline-, glycine-, tyrosine-rich sequence with bacterial and tissue collagenase. J Biol Chem. 1993;268:26704-11 pubmed
    ..Hence, L-29 is a substrate for bacterial and tissue collagenases even though the R-domain is non-collagenous. Moreover, the co-purification suggests a non-enzymatic interaction between 92-kDa collagenase and L-29. ..
  45. Jordan G, Carson C, Lipshultz L. Minimally invasive treatment of Peyronie's disease: evidence-based progress. BJU Int. 2014;114:16-24 pubmed publisher
    ..Treatments that have decreased penile curvature deformity in Level 1 or Level 2 evidence-based, placebo-controlled studies include intralesional injection with interferon ?-2b or collagenase clostridium histolyticum. ..
  46. Spiro R. Studies on the renal glomerular basement membrane. Nature of the carbohydrate units and their attachment to the peptide portion. J Biol Chem. 1967;242:1923-32 pubmed
  47. Fini M, Plucinska I, Mayer A, Gross R, Brinckerhoff C. A gene for rabbit synovial cell collagenase: member of a family of metalloproteinases that degrade the connective tissue matrix. Biochemistry. 1987;26:6156-65 pubmed
    ..We have further sequenced genomic DNA flanking the collagenase gene and have identified nucleic acid elements of possible importance in gene regulation. ..
  48. Erdeve O, Atasay B, Arsan S. Collagenase application for amputation in a preterm. Pediatr Dermatol. 2007;24:195-6 pubmed
  49. Van Wart H, Birkedal Hansen H. The cysteine switch: a principle of regulation of metalloproteinase activity with potential applicability to the entire matrix metalloproteinase gene family. Proc Natl Acad Sci U S A. 1990;87:5578-82 pubmed
    ..Since conditions in different cells and tissues may match those necessary to effect one of these activation modes for a given MMP, this may offer metabolic flexibility in the control of MMP activation. ..
  50. Aysan E, Bektas H, Ersoz F, Behzat K. Role of single-dose clostridiopeptidase A collagenase in peritoneal adhesions. Eur Surg Res. 2011;47:130-4 pubmed publisher
    ..5 ± 0.52, and 1.3 ± 0.67, respectively (p< 0.0001). The group 4 score was lower than those of groups 2 (p = 0.01) and 3 (p = 0.025). A single dose of CAC reduces PPA formation. CAC, however, is not effective on already formed PPAs. ..
  51. Koyanagi T. [A biochemical analysis of experimental chemonucleolysis]. Nihon Seikeigeka Gakkai Zasshi. 1989;63:549-61 pubmed
    ..These findings suggest that the shock-absorbing ability of enzyme-injected discs does not recover. ..
  52. Malfroy B, Kado Fong H, Gros C, Giros B, Schwartz J, Hellmiss R. Molecular cloning and amino acid sequence of rat kidney aminopeptidase M: a member of a super family of zinc-metallohydrolases. Biochem Biophys Res Commun. 1989;161:236-41 pubmed
    ..Rat aminopeptidase M shows 77% similarity with the recently cloned human enzyme, as well as weaker but significant similarity with aminopeptidase N from E. coli (18%) and with human leukotriene A4 hydrolase (21%). ..
  53. Whitham S, Murphy G, Angel P, Rahmsdorf H, Smith B, Lyons A, et al. Comparison of human stromelysin and collagenase by cloning and sequence analysis. Biochem J. 1986;240:913-6 pubmed