PDBsum entry 4p3c

Immune system

PDB id: 4p3c

Contents

Protein chains

218 a.a.

218 a.a.

13 a.a.

Ligands

EPE

EDO ×6

ACT ×3

Metals

_CL

_MG

Waters ×388

PDB id:

4p3c

Name:

Immune system

Title:

Mt1-mmp:fab complex (form i)

Structure:

Heavy chain fab fragment of antibody lem-2/15. Chain: h. Fragment: mt1-mmp v-b loop. Engineered: yes. Light chain fab fragment of antibody lem-2/15. Chain: l. Engineered: yes. Matrix metalloproteinase-14. Chain: m.

Source:

Mus musculus. Organism_taxid: 10090. Expressed in: escherichia coli. Expression_system_taxid: 562. Homo sapiens. Human. Organism_taxid: 9606. Gene: mmp14. Expression_system_taxid: 511693.

Resolution:

1.94Å R-factor: 0.156 R-free: 0.200

Authors:

H.Rozenberg,Y.Udi,I.Sagi

Key ref:

Y.Udi et al. (2015). Inhibition mechanism of membrane metalloprotease by an exosite-swiveling conformational antibody. Structure, 23, 104-115. PubMed id: 25482542 DOI: 10.1016/j.str.2014.10.012

Date:

06-Mar-14 Release date: 17-Dec-14

Protein chain

No UniProt id for this chain

Struc: 218 a.a.

Protein chain

No UniProt id for this chain

Struc: 218 a.a.

Protein chain

P50281  (MMP14_HUMAN) -  Matrix metalloproteinase-14 from Homo sapiens

Seq: 582 a.a.

Struc: 13 a.a.

Enzyme reactions

• Enzyme class: Chain M: E.C.3.4.24.80 - membrane-type matrix metalloproteinase-1.
• Cofactor: Zn(2+)

DOI no: 10.1016/j.str.2014.10.012

Structure 23:104-115 (2015)

PubMed id: 25482542

Inhibition mechanism of membrane metalloprotease by an exosite-swiveling conformational antibody.

Y.Udi, M.Grossman, I.Solomonov, O.Dym, H.Rozenberg, V.Moreno, P.Cuniasse, V.Dive, A.G.Arroyo, I.Sagi.

ABSTRACT

Membrane type 1 metalloprotease (MT1-MMP) is a membrane-anchored, zinc-dependent protease. MT1-MMP is an important mediator of cell migration and invasion, and overexpression of this enzyme has been correlated with the malignancy of various tumor types. Therefore, modulators of MT1-MMP activity are proposed to possess therapeutic potential in numerous invasive diseases. Here we report the inhibition mode of MT1-MMP by LEM-2/15 antibody, which targets a surface epitope of MT1-MMP. Specifically, the crystal structures of Fab LEM-2/15 in complex with the MT1-MMP surface antigen suggest that conformational swiveling of the enzyme surface loop is required for effective binding and consequent inhibition of MT1-MMP activity on the cell membrane. This inhibition mechanism appears to be effective in controlling active MT1-MMP in endothelial cells and at the leading edge of migratory cancer cells.