4FU4: Human Collagenase 3 (mmp-13) With Peptide From Pro-domain

Citation:
Abstract
Matrix metalloproteinase (MMP)-13 is one of the mammalian collagenases that play key roles in tissue remodelling and repair and in progression of diseases such as cancer, arthritis, atherosclerosis, and aneurysm. For collagenase to cleave triple helical collagens, the triple helical structure has to be locally unwound before hydrolysis, but this process is not well understood. We report crystal structures of catalytically inactive full-length human MMP-13(E223A) in complex with peptides of 14-26 aa derived from the cleaved prodomain during activation. Peptides are bound to the active site of the enzyme by forming an extended beta-strand with Glu(40) or Tyr(46) inserted into the S1' specificity pocket. The structure of the N-terminal part of the peptides is variable and interacts with different parts of the catalytic domain. Those areas are designated substrate-dependent exosites, in that they accommodate different peptide structures, whereas the precise positioning of the substrate backbone is maintained in the active site. These modes of peptide-MMP-13 interactions have led us to propose how triple helical collagen strands fit into the active site cleft of the collagenase.
PDB ID: 4FU4Download
MMDB ID: 112770
PDB Deposition Date: 2012/6/28
Updated in MMDB: 2013/08
Experimental Method:
x-ray diffraction
Resolution: 2.85  Å
Source Organism:
Similar Structures:
Biological Unit for 4FU4: dimeric; determined by author and by software (PISA)
Molecular Components in 4FU4
Label Count Molecule
Proteins (2 molecules)
1
Collagenase 3(Gene symbol: MMP13)
Molecule annotation
1
Collagenase 3, Pro-domain Peptide(Gene symbol: MMP13)
Molecule annotation
Chemicals (21 molecules)
1
2
2
4
3
2
4
13
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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