4G0D

Human collagenase 3 (MMP-13) full form with peptides from pro-domain

Summary for 4G0D

• Entry DOI: 10.2210/pdb4g0d/pdb
• Related: 1PEX 3TVC 4FU4 4FVL
• Descriptor: Collagenase 3, Collagenase 3, pro-domain peptide, ZINC ION, ... (9 entities in total)
• Functional Keywords: protein-peptide complex, collagenase, cleavage with mmp3, hydrolase, pro-peptide, metzincin, zinc metalloprotease, collagen cleavage, collagen
• Biological source: Homo sapiens (human); More
• Cellular location: Secreted, extracellular space, extracellular matrix (Probable): P45452 P45452
• Total number of polymer chains: 8
• Total formula weight: 187080.52

Authors

Stura, E.A.,Vera, L.,Visse, R.,Nagase, H.,Dive, V. (deposition date: 2012-07-09, release date: 2013-08-21, Last modification date: 2023-09-13)

Primary citation

Stura, E.A.,Visse, R.,Cuniasse, P.,Dive, V.,Nagase, H.
Crystal structure of full-length human collagenase 3 (MMP-13) with peptides in the active site defines exosites in the catalytic domain.
Faseb J., 27:4395-4405, 2013

PubMed 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 β-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.

PubMed: 23913860
DOI: 10.1096/fj.13-233601

Experimental method

X-RAY DIFFRACTION (2.54 Å)