2MZE: NMR Solution Structure of the PRO Form of Human Matrilysin (proMMP-7)

Matrix metalloproteinase-7 (MMP-7) sheds signaling proteins from cell surfaces to activate bacterial killing, wound healing, and tumorigenesis. The mechanism targeting soluble MMP-7 to membranes has been investigated. Nuclear magnetic resonance structures of the zymogen, free and bound to membrane mimics without and with anionic lipid, reveal peripheral binding to bilayers through paramagnetic relaxation enhancements. Addition of cholesterol sulfate partially embeds the protease in the bilayer, restricts its diffusion, and tips the active site away from the bilayer. Its insertion of hydrophobic residues organizes the lipids, pushing the head groups and sterol sulfate outward toward the enzyme's positive charge on the periphery of the enlarged interface. Fluorescence probing demonstrates a similar mode of binding to plasma membranes and internalized vesicles of colon cancer cells. Binding of bilayered micelles induces allosteric activation and conformational change in the auto-inhibitory peptide and the adjacent scissile site, illustrating a potential intermediate in the activation of the zymogen.
PDB ID: 2MZEDownload
MMDB ID: 134002
PDB Deposition Date: 2015/2/11
Updated in MMDB: 2015/11
Experimental Method:
solution nmr
Source Organism:
Similar Structures:
Biological Unit for 2MZE: monomeric; determined by author and by software (PISA)
Molecular Components in 2MZE
Label Count Molecule
Protein (1 molecule)
Matrilysin(Gene symbol: MMP7)
Molecule annotation
Chemicals (4 molecules)
* Click molecule labels to explore molecular sequence information.

Citing MMDB