Human and mouse homo-oligomeric meprin A metalloendopeptidase: Substrate and inhibitor specificities

John E. Bylander, Greg P. Bertenshaw, Gail L. Matters, Simon J. Hubbard, Judith S. Bond

Research output: Contribution to journalArticlepeer-review

13 Scopus citations


Meprin metalloproteinases have been implicated in the susceptibility to and progression of diabetic nephropathy and inflammatory bowel diseases. Our studies with experimental models of these diseases in mice are congruent with the conclusion that meprins modulate the inflammatory responses and tissue damage. To determine whether the mouse and human enzymes differ, recombinant forms of meprin A from the two species were compared with respect to structure, substrates and inhibitors. Human homo-oligomeric meprin A formed oligomers ranging from 950 000 to 1 500 000 Da vs. 900 000 Da for mouse meprin A. Human and mouse meprin A exhibited similar activity against azocasein, fibronectin, collagen IV, and peptides such as parathyroid hormone, ghrelin, and gastrin-releasing peptide. The human enzyme had lower activity against gelatin, bradykinin, α-melanocyte-stimulating hormone and neurotensin, and higher activity against secretin and orcokinin. Human meprin A showed a preference for acidic residues in the P1′ position of the substrate, unlike mouse meprin A. Several metalloproteinase inhibitors had IC50 values in the nanomolar range, but potency ranged from similar values to a difference of several orders of magnitude for meprins from the two species. This work provides valuable data to improve predictability for human systems based on meprin functions in mouse models.

Original languageEnglish (US)
Pages (from-to)1163-1172
Number of pages10
JournalBiological Chemistry
Issue number11
StatePublished - Nov 1 2007

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Clinical Biochemistry


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