Characterisation of the MMP‐12–Elastin Adduct

Abstract

Dedicated to the Centenary of the Italian Chemical Society MMP-12 (matrix metalloproteinase 12)is an important protein of the MMP family. [1][2][3][4] Its substrate is elastin, [5][6][7][8] which is composed of a cross-linked insoluble network of polypeptide chains of tropoelastin of MW 65 kDa each. [9] Insoluble elastin is responsible for keeping some extracellular connective tissues elastic.The full-length MMP-12 is made up by a catalytic (CAT) domain and a hemopexin-like (HPX) domain. The two domains have relatively large conformational freedom, [10] as also recently found in MMP-1 [11] and MMP-9. [12] The role of the HPX domain is not certain, as the CAT domain is always active by itself, [13] even if it may have a smaller turnover for some substrates. [14] Experimental structures and models, representative of the binding mode of peptide substrates on protein active site are already present in the Protein Data Bank. However, the interaction of native elastin with full length MMP-12 and its [a] Prof.

1H-detected solid-state NMR of proteins entrapped in bioinspired silica: a new tool for biomaterials characterization

“…The catalytic domain of MMP-12 (catMMP12) has been expressed as fusion protein with a R5 peptide at the C-terminus as already described62.…”

Matrix metalloproteinase interactions with collagen and elastin

“…While solubilized elastin interacts with both catalytic and HPX domains of MMP-12 [75], the catalytic domain is sufficient for elastolysis by MMP-12 [58]. Ten residues on the periphery of the active site cleft were found to contribute to the specific activity of MMP-12 towards an enhanced elastin substrate and to distinguish it from other MMPs [58] (Fig.…”

“…The two residues nearest the catalytic center boost the rate of catalytic turnover of the elastin substrate, whereas the eight residues more distant instead enhance the K m or apparent affinity [58]. Multiple elastin-derived peptides were proposed to bind the full length of the active site cleft of MMP-12 in an extended conformation [75]. Such modes of binding place peptides between the nine residues bordering the cleft implicated in elastolysis (Fig.…”

The cell-elastin-elastase(s) interacting triade directs elastolysis

“…Recently, the interaction of MMP-12 with elastin has been studied by nuclear magnetic resonance (NMR). Data showed that the catalytic domain of the enzyme was able to bind directly to its natural substrate since affected nuclei ( 13 C, 2 H, 15 N) following enzyme-elastin interaction all belong to active crevice of MMP-12 (66).…”