Nucleic acid-induced potentiation of matrix metalloproteinase-9 enzymatic activity

Tyler Duellman, Xi Chen, Rie Wakamiya, Jay Yang

Research output: Contribution to journalArticle

Abstract

Matrix metalloproteinases (MMPs) play varied roles in normal biology and diseases where, depending on the context, both inhibition and enhancement of the enzymatic activity may be beneficial. However, there are very few reports of positive modulators of MMP activity. We report that polynucleotides, including single-stranded DNA, RNA, and even double-stranded DNA, bind to and enhance the enzymatic activity of MMP9. This enhancement of MMP9 catalytic activity is not shared by biologically active polycationic molecules suggesting nonspecific charge screening as an unlikely mechanism. Deletion construct and MMP1, 2, and 3 studies suggest that the type-II fibronectin repeat domains of the enzyme appear to play a role in mediating the nucleotide potentiation of MMP9 activity. Single-stranded DNA enhances nerve growth factor-induced MMP9-dependent neurite extension in pheochromocytoma 12 cells providing evidence for potential biological significance of the nucleotide-mediated allosteric enhancement of the catalytic activity.

Original languageEnglish
Pages (from-to)1597-1610
Number of pages14
JournalBiochemical Journal
Volume475
Issue number9
DOIs
Publication statusPublished - 2018 May 15
Externally publishedYes

Fingerprint

Single-Stranded DNA
Matrix Metalloproteinase 9
Matrix Metalloproteinases
Nucleic Acids
Catalyst activity
Nucleotides
Polynucleotides
Pheochromocytoma
Nerve Growth Factor
Neurites
Fibronectins
Modulators
Screening
RNA
Molecules
DNA
Enzymes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Nucleic acid-induced potentiation of matrix metalloproteinase-9 enzymatic activity. / Duellman, Tyler; Chen, Xi; Wakamiya, Rie; Yang, Jay.

In: Biochemical Journal, Vol. 475, No. 9, 15.05.2018, p. 1597-1610.

Research output: Contribution to journalArticle

Duellman, Tyler ; Chen, Xi ; Wakamiya, Rie ; Yang, Jay. / Nucleic acid-induced potentiation of matrix metalloproteinase-9 enzymatic activity. In: Biochemical Journal. 2018 ; Vol. 475, No. 9. pp. 1597-1610.
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