DrugBank: Collagenase (DB00048)

targets (4)

Identification

Name

Collagenase

Accession Number

DB00048 (BIOD00010, BTD00010)

Type

biotech

Groups

approved

Description

The enzyme collagenase is derived from fermentation of Clostridium histolyticum

Protein structure

Display: 3D Structure

Protein chemical formula

C₅₀₂₈H₇₆₆₆N₁₃₀₀O₁₅₆₄S₂₁

Protein average weight

112023.2000

Sequences

>DB00048 sequence
VQNESKRYTVSYLKTLNYYDLVDLLVKTEIENLPDLFQYSSDAKEFYGNKTRMSFIMDEI
GRRAPQYTEIDHKGIPTLVEVVRAGFYLGFHNKELNEINKRSFKERVIPSILAIQKNPNF
KLGTEVQDKIVSATGLLAGNETAPPEVVNNFTPILQDCIKNIDRYALDDLKSKALFNVLA
APTYDITEYLRATKEKPENTPWYGKIDGFINELKKLALYGKINDNNSWIIDNGIYHIAPL
GKLHSNNKIGIETLTEVMKVYPYLSMQHLQSADQIKRHYDSKDAEGNKIPLDKFKKEGKE
KYCPKTYTFDDGKVIIKAGARVEEEKVKRLYWASKEVNSQFFRVYGIDKPLEEGNPDDIL
TMVIYNSPEEYKLNSVLYGYDTNNGGMYIEPEGTFFTYEREAQESTYTLEELFRHEYTHY
LQGRYAVPGQWGRTKLYDNDRLTWYEEGGAELFAGSTRTSGILPRKSIVSNIHNTTRNNR
YKLSDTVHSKYGASFEFYNYACMFMDYMYNKDMGILNKLNDLAKNNDVDGYDNYIRDLSS
NYALNDKYQDHMQERIDNYENLTVPFVADDYLVRHAYKNPNEIYSEISEVAKLKDAKSEV
KKSQYFSTFTLRGSYTGGASKGKLEDQKAMNKFIDDSLKKLDTYSWSGYKTLTAYFTNYK
VDSSNRVTYDVVFHGYLPNEGDSKNSLPYGKINGTYKGTEKEKIKFSSEGSFDPDGKIVS
YEWDFGDGNKSNEENPEHSYDKVGTYTVKLKVTDDKGESSVSTTTAEIKDLSENKLPVIY
MHVPKSGALNQKVVFYGKGTYDPDGSIAGYQWDFGDGSDFSSEQNPSHVYTKKGEYTVTL
RVMDSSGQMSEKTMKIKITDPVYPIGTEKEPNNSKETASGPIVPGIPVSGTIENTSDQDY
FYFDVITPGEVKIDINKLGYGGATWVVYDENNNAVSYATDDGQNLSGKFKADKPGRYYIH
LYMFNGSYMPYRINIEGSVGR

FASTA

Synonyms

AA4500

Salts

Not Available

Brand names

Name	Company
Cordase
Santyl (Advance Biofactures Corp)
Xiaflextm

Brand mixtures

Not Available

Categories

Anti-Ulcer Agents
Topical

CAS number

9001-12-1

Taxonomy

Kingdom

Not Available

Classes

Not Available

Substructures

Not Available

Pharmacology

Indication

Used to promote debridement of necrotic tissue in the treatment of severe burns and dermal ulcers including decubitus ulcers.

Pharmacodynamics

Used in the treatment of skin ulcers and sever burns, collagenase is able to digest collagen in necrotic tissue at physiological pH by hydrolyzing the peptide bonds of undenatured and denatured collagen. Collagenase thus contributes towards the formation of granulation tissue and subsequent epithelization of dermal ulcers and severely burned areas. The action of collagenase may remove substrates necessary for bacterial proliferation or may permit antibodies, leukocytes, and antibiotics better access to the infected area.

Mechanism of action

Collagenase is a protease that is specific to collagen. The triple helical region of interstitial collagens is highly resistant to most cell proteinases. However, during remodeling of the connective tissue in such processes as wound healing and metastasis, collagen becomes susceptible to cleavage by collagenases. Collagenase cleaves all 3 alpha helical chains of native Types I, II and III collagens at a single locus by hydrolyzing the peptide bond following the Gly residue of the sequence: Gly 775-(Ile or Leu) 776-(Ala or Leu) 777 located approximately three-fourths of the chain length from each N-terminus

Absorption

Not Available

Volume of distribution

Not Available

Protein binding

Not Available

Metabolism

Not Available

Route of elimination

Not Available

Half life

Not Available

Clearance

Not Available

Toxicity

Not Available

Affected organisms

Humans and other mammals

Pathways

Not Available

Pharmacoeconomics

Manufacturers

Not Available

Packagers

Dosage forms

Form	Route	Strength
Ointment	Topical

Prices

Unit description	Cost	Unit
Xiaflex 0.9 mg vial	3900.0 USD	vial
Collagenase powder	2432.7 USD	g
Santyl 250 unit/gm Ointment 15 gm Tube	62.98 USD	tube
Santyl ointment	4.13 USD	g

DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.

Patents

Not Available

Properties

State

liquid

Experimental Properties

Property	Value	Source
hydrophobicity	-0.714	Not Available
isoelectric point	5.58	Not Available

References

Synthesis Reference

Not Available

General Reference

Norris DB, Trudgill PW: Multiple forms of cyclohexanone oxygenase from Nocardia globerula CL1. Eur J Biochem. 1976 Mar 16;63(1):193-8. Pubmed
Pajot P: Fluroescence of proteins in 6-M guanidine hydrochloride. A method for the quantitative determination of tryptophan. Eur J Biochem. 1976 Mar 16;63(1):263-9. Pubmed

External Links

Resource	Link
PharmGKB	PA449107
Drug Product Database	2063670
RxList	http://www.rxlist.com/cgi/generic3/collagenase.htm
Drugs.com	http://www.drugs.com/cdi/collagenase-ointment.html
Wikipedia	http://en.wikipedia.org/wiki/Collagenase

ATC Codes

D03BA02

AHFS Codes

84:92.00

PDB Entries

1NQD

FDA label

Not Available

MSDS

show (72.9 KB)

Interactions

Drug Interactions

Searched, but no interactions found.

Food Interactions

Not Available

Targets
1. Collagen alpha-1(I) chain Pharmacological action: unknown Type I collagen is a member of group I collagen (fibrillar forming collagen) Organism class: human UniProt ID: P02452 Gene: COL1A1 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Egeblad M, Shen HC, Behonick DJ, Wilmes L, Eichten A, Korets LV, Kheradmand F, Werb Z, Coussens LM: Type I collagen is a genetic modifier of matrix metalloproteinase 2 in murine skeletal development. Dev Dyn. 2007 Jun;236(6):1683-93. Pubmed Lindsey ML, Yoshioka J, MacGillivray C, Muangman S, Gannon J, Verghese A, Aikawa M, Libby P, Krane SM, Lee RT: Effect of a cleavage-resistant collagen mutation on left ventricular remodeling. Circ Res. 2003 Aug 8;93(3):238-45. Epub 2003 Jul 10. Pubmed Beare AH, O’Kane S, Krane SM, Ferguson MW: Severely impaired wound healing in the collagenase-resistant mouse. J Invest Dermatol. 2003 Jan;120(1):153-63. Pubmed Chiu CJ, Chang ML, Chiang CP, Hahn LJ, Hsieh LL, Chen CJ: Interaction of collagen-related genes and susceptibility to betel quid-induced oral submucous fibrosis. Cancer Epidemiol Biomarkers Prev. 2002 Jul;11(7):646-53. Pubmed Beare AH, Krane SM, Ferguson MW: Variable impairment of wound healing in the heterozygous collagenase-resistant mouse. Wound Repair Regen. 2005 Jan-Feb;13(1):27-40. Pubmed 2. Collagen alpha-1(II) chain Pharmacological action: unknown Collagen type II is specific for cartilaginous tissues. It is essential for the normal embryonic development of the skeleton, for linear growth and for the ability of cartilage to resist compressive forces Organism class: human UniProt ID: P02458 Gene: COL2A1 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Fraser A, Fearon U, Billinghurst RC, Ionescu M, Reece R, Barwick T, Emery P, Poole AR, Veale DJ: Turnover of type II collagen and aggrecan in cartilage matrix at the onset of inflammatory arthritis in humans: relationship to mediators of systemic and local inflammation. Arthritis Rheum. 2003 Nov;48(11):3085-95. Pubmed Imai K, Dalal SS, Hambor J, Mitchell P, Okada Y, Horton WC, D’Armiento J: Bone growth retardation in mouse embryos expressing human collagenase 1. Am J Physiol Cell Physiol. 2007 Oct;293(4):C1209-15. Epub 2007 Jul 25. Pubmed Verstappen SM, Poole AR, Ionescu M, King LE, Abrahamowicz M, Hofman DM, Bijlsma JW, Lafeber FP: Radiographic joint damage in rheumatoid arthritis is associated with differences in cartilage turnover and can be predicted by serum biomarkers: an evaluation from 1 to 4 years after diagnosis. Arthritis Res Ther. 2006;8(1):R31. Epub 2006 Jan 10. Pubmed Martin G, Bogdanowicz P, Domagala F, Ficheux H, Pujol JP: Articular chondrocytes cultured in hypoxia: their response to interleukin-1beta and rhein, the active metabolite of diacerhein. Biorheology. 2004;41(3-4):549-61. Pubmed Pratta MA, Yao W, Decicco C, Tortorella MD, Liu RQ, Copeland RA, Magolda R, Newton RC, Trzaskos JM, Arner EC: Aggrecan protects cartilage collagen from proteolytic cleavage. J Biol Chem. 2003 Nov 14;278(46):45539-45. Epub 2003 Jul 30. Pubmed 3. Collagen alpha-1(III) chain Pharmacological action: unknown Collagen type III occurs in most soft connective tissues along with type I collagen Organism class: human UniProt ID: P02461 Gene: COL3A1 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed Cole WG, Chiodo AA, Lamande SR, Janeczko R, Ramirez F, Dahl HH, Chan D, Bateman JF: A base substitution at a splice site in the COL3A1 gene causes exon skipping and generates abnormal type III procollagen in a patient with Ehlers-Danlos syndrome type IV. J Biol Chem. 1990 Oct 5;265(28):17070-7. Pubmed 4. Collagen alpha-2(I) chain Pharmacological action: unknown Type I collagen is a member of group I collagen (fibrillar forming collagen) Organism class: human UniProt ID: P08123 Gene: COL1A2 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Chiu CJ, Chang ML, Chiang CP, Hahn LJ, Hsieh LL, Chen CJ: Interaction of collagen-related genes and susceptibility to betel quid-induced oral submucous fibrosis. Cancer Epidemiol Biomarkers Prev. 2002 Jul;11(7):646-53. Pubmed

Targets

1. Collagen alpha-1(I) chain

Pharmacological action: unknown

Type I collagen is a member of group I collagen (fibrillar forming collagen)

Organism class: human
UniProt ID: P02452 Link_out

Gene: COL1A1 Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

Egeblad M, Shen HC, Behonick DJ, Wilmes L, Eichten A, Korets LV, Kheradmand F, Werb Z, Coussens LM: Type I collagen is a genetic modifier of matrix metalloproteinase 2 in murine skeletal development. Dev Dyn. 2007 Jun;236(6):1683-93. Pubmed
Lindsey ML, Yoshioka J, MacGillivray C, Muangman S, Gannon J, Verghese A, Aikawa M, Libby P, Krane SM, Lee RT: Effect of a cleavage-resistant collagen mutation on left ventricular remodeling. Circ Res. 2003 Aug 8;93(3):238-45. Epub 2003 Jul 10. Pubmed
Beare AH, O’Kane S, Krane SM, Ferguson MW: Severely impaired wound healing in the collagenase-resistant mouse. J Invest Dermatol. 2003 Jan;120(1):153-63. Pubmed
Chiu CJ, Chang ML, Chiang CP, Hahn LJ, Hsieh LL, Chen CJ: Interaction of collagen-related genes and susceptibility to betel quid-induced oral submucous fibrosis. Cancer Epidemiol Biomarkers Prev. 2002 Jul;11(7):646-53. Pubmed
Beare AH, Krane SM, Ferguson MW: Variable impairment of wound healing in the heterozygous collagenase-resistant mouse. Wound Repair Regen. 2005 Jan-Feb;13(1):27-40. Pubmed

2. Collagen alpha-1(II) chain

Pharmacological action: unknown

Collagen type II is specific for cartilaginous tissues. It is essential for the normal embryonic development of the skeleton, for linear growth and for the ability of cartilage to resist compressive forces

Organism class: human
UniProt ID: P02458 Link_out

Gene: COL2A1 Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

Fraser A, Fearon U, Billinghurst RC, Ionescu M, Reece R, Barwick T, Emery P, Poole AR, Veale DJ: Turnover of type II collagen and aggrecan in cartilage matrix at the onset of inflammatory arthritis in humans: relationship to mediators of systemic and local inflammation. Arthritis Rheum. 2003 Nov;48(11):3085-95. Pubmed
Imai K, Dalal SS, Hambor J, Mitchell P, Okada Y, Horton WC, D’Armiento J: Bone growth retardation in mouse embryos expressing human collagenase 1. Am J Physiol Cell Physiol. 2007 Oct;293(4):C1209-15. Epub 2007 Jul 25. Pubmed
Verstappen SM, Poole AR, Ionescu M, King LE, Abrahamowicz M, Hofman DM, Bijlsma JW, Lafeber FP: Radiographic joint damage in rheumatoid arthritis is associated with differences in cartilage turnover and can be predicted by serum biomarkers: an evaluation from 1 to 4 years after diagnosis. Arthritis Res Ther. 2006;8(1):R31. Epub 2006 Jan 10. Pubmed
Martin G, Bogdanowicz P, Domagala F, Ficheux H, Pujol JP: Articular chondrocytes cultured in hypoxia: their response to interleukin-1beta and rhein, the active metabolite of diacerhein. Biorheology. 2004;41(3-4):549-61. Pubmed
Pratta MA, Yao W, Decicco C, Tortorella MD, Liu RQ, Copeland RA, Magolda R, Newton RC, Trzaskos JM, Arner EC: Aggrecan protects cartilage collagen from proteolytic cleavage. J Biol Chem. 2003 Nov 14;278(46):45539-45. Epub 2003 Jul 30. Pubmed

3. Collagen alpha-1(III) chain

Pharmacological action: unknown

Collagen type III occurs in most soft connective tissues along with type I collagen

Organism class: human
UniProt ID: P02461 Link_out

Gene: COL3A1 Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
Cole WG, Chiodo AA, Lamande SR, Janeczko R, Ramirez F, Dahl HH, Chan D, Bateman JF: A base substitution at a splice site in the COL3A1 gene causes exon skipping and generates abnormal type III procollagen in a patient with Ehlers-Danlos syndrome type IV. J Biol Chem. 1990 Oct 5;265(28):17070-7. Pubmed

4. Collagen alpha-2(I) chain

Pharmacological action: unknown

Type I collagen is a member of group I collagen (fibrillar forming collagen)

Organism class: human
UniProt ID: P08123 Link_out

Gene: COL1A2 Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

Chiu CJ, Chang ML, Chiang CP, Hahn LJ, Hsieh LL, Chen CJ: Interaction of collagen-related genes and susceptibility to betel quid-induced oral submucous fibrosis. Cancer Epidemiol Biomarkers Prev. 2002 Jul;11(7):646-53. Pubmed

Comments

Drug created on June 13, 2005 07:24 / Updated on September 03, 2011 16:33