The fibronectin-like domain is required for the type V and XI collagenolytic activity of gelatinase B

Thomas J. O'Farrell, Tayebeh Pourmotabbed

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Gelatinase B (matrix metalloproteinase-9) is able to degrade several extracellular matrix proteins, including gelatin, elastin, and collagen types IV, V, XI, and XIV. This enzyme contains a 'fibronectin-like' domain which is composed of three tandem copies of a fibronectin type 2 homology unit inserted into its catalytic domain. We have studied the involvement of this domain in the substrate specificity of gelatinase B by expressing a mutant of the enzyme, in Escherichia coli, in which this domain has been deleted. This mutant enzyme retained its ability to cleave the peptide substrate Mca- PLGL(Dpa)ARNH2, possessing K(m) and k(cat) values similar to those of the wild-type enzyme. In addition, the NH2-terminal, 14-kDa, inhibitory domain of recombinant tissue inhibitor of metalloproteinase-2 was able to inhibit the mutant and the wild-type enzymes with the same potency. The mutant's gelatinolytic activity was also retained but reduced in comparison to that of the wild-type enzyme. However, contrary to the wildtype enzyme, the mutant was not able to digest or bind fibrillar collagen types V and XI. These data indicate that the fibronectin-like domain of gelatinase B is an important determinant of the enzyme's fibrillar collagen substrate specificity. It allows the enzyme to bind to and cleave collagen types V and XI, events which are thought to be involved in several normal physiological and pathological processes such as metastasis and arthritis.

Original languageEnglish (US)
Pages (from-to)24-30
Number of pages7
JournalArchives of Biochemistry and Biophysics
Volume354
Issue number1
DOIs
StatePublished - Jun 1 1998

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Matrix Metalloproteinase 9
Fibronectins
Enzymes
Collagen Type V
Collagen Type XI
Fibrillar Collagens
Substrate Specificity
Substrates
Physiological Phenomena
Tissue Inhibitor of Metalloproteinase-2
Collagen Type IV
Elastin
Extracellular Matrix Proteins
Pathologic Processes
Gelatin
Escherichia coli
Arthritis
Catalytic Domain
Neoplasm Metastasis
Peptides

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology

Cite this

The fibronectin-like domain is required for the type V and XI collagenolytic activity of gelatinase B. / O'Farrell, Thomas J.; Pourmotabbed, Tayebeh.

In: Archives of Biochemistry and Biophysics, Vol. 354, No. 1, 01.06.1998, p. 24-30.

Research output: Contribution to journalArticle

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