PDBsum entry 2mls

Hydrolase

PDB id: 2mls

Contents

Protein chain

164 a.a.

Ligands

PX4 ×125

Metals

_ZN ×2

_CA ×3

PDB id:

2mls

Name:

Hydrolase

Title:

Membrane bilayer complex with matrix metalloproteinase-12 at its beta- face

Structure:

Macrophage metalloelastase. Chain: a. Synonym: mme, macrophage elastase, me, hme, matrix metalloproteinase- 12, mmp-12. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: mmp12, hme. Expressed in: escherichia coli. Expression_system_taxid: 562.

NMR struc:

14 models

Authors:

R.K.Koppisetti,Y.G.Fulcher,S.H.Prior,M.Lenoir,M.Overduin,S.R.Van Doren

Key ref:

R.K.Koppisetti et al. (2014). Ambidextrous binding of cell and membrane bilayers by soluble matrix metalloproteinase-12. Nat Commun, 5, 5552. PubMed id: 25412686 DOI: 10.1038/ncomms6552

Date:

04-Mar-14 Release date: 03-Dec-14

Protein chain

P39900  (MMP12_HUMAN) -  Macrophage metalloelastase from Homo sapiens

Seq: 470 a.a.

Struc: 164 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class: E.C.3.4.24.65 - macrophage elastase.
• Reaction: Hydrolysis of soluble and insoluble elastin. Specific cleavages are also produced at 14-Ala-|-Leu-15 and 16-Tyr-|-Leu-17 in the B chain of insulin.
• Cofactor: Ca(2+); Zn(2+)

DOI no: 10.1038/ncomms6552

Nat Commun 5:5552 (2014)

PubMed id: 25412686

Ambidextrous binding of cell and membrane bilayers by soluble matrix metalloproteinase-12.

R.K.Koppisetti, Y.G.Fulcher, A.Jurkevich, S.H.Prior, J.Xu, M.Lenoir, M.Overduin, S.R.Van Doren.

ABSTRACT

Matrix metalloproteinases (MMPs) regulate tissue remodelling, inflammation and disease progression. Some soluble MMPs are inexplicably active near cell surfaces. Here we demonstrate the binding of MMP-12 directly to bilayers and cellular membranes using paramagnetic NMR and fluorescence. Opposing sides of the catalytic domain engage spin-labelled membrane mimics. Loops project from the β-sheet interface to contact the phospholipid bilayer with basic and hydrophobic residues. The distal membrane interface comprises loops on the other side of the catalytic cleft. Both interfaces mediate MMP-12 association with vesicles and cell membranes. MMP-12 binds plasma membranes and is internalized to hydrophobic perinuclear features, the nuclear membrane and inside the nucleus within minutes. While binding of TIMP-2 to MMP-12 hinders membrane interactions beside the active site, TIMP-2-inhibited MMP-12 binds vesicles and cells, suggesting compensatory rotation of its membrane approaches. MMP-12 association with diverse cell membranes may target its activities to modulate innate immune responses and inflammation.