PDBsum entry: 1cxv

Hydrolase

PDB id: 1cxv

Contents

Protein chains

160 a.a. *

Ligands

CBP ×2

Metals

_ZN ×4

_CA ×4

Waters ×321

* Residue conservation analysis

PDB id:

1cxv

Name:

Hydrolase

Title:

Structure of recombinant mouse collagenase-3 (mmp-13)

Structure:

Protein (collagenase-3). Chain: a, b. Fragment: catalytic domain. Synonym: matrix metalloproteinase, mmp-13. Ec: 3.4.24.-

Source:

Mus musculus. House mouse. Organism_taxid: 10090

Biol. unit:

Dimer (from PQS)

Resolution:

2.00Å R-factor: 0.196 R-free: 0.234

Authors:

I.Botos,E.Meyer,S.M.Swanson,V.Lemaitre,Y.Eeckhout,E.F.Meyer

Key ref:

I.Botos et al. (1999). Structure of recombinant mouse collagenase-3 (MMP-13). J Mol Biol, 292, 837-844. PubMed id: 10525409 DOI: 10.1006/jmbi.1999.3068

Date:

30-Aug-99 Release date: 30-Aug-00

Protein chains

P33435  (MMP13_MOUSE) -  Collagenase 3

Seq: 472 a.a.

Struc: 160 a.a.

 Gene Ontology (GO) functional annotation 

• Cellular component: extracellular matrix (1 term)
• Biological process: proteolysis (1 term)
• Biochemical function: metallopeptidase activity (3 terms)

DOI no: 10.1006/jmbi.1999.3068

J Mol Biol 292:837-844 (1999)

PubMed id: 10525409

Structure of recombinant mouse collagenase-3 (MMP-13).

I.Botos, E.Meyer, S.M.Swanson, V.Lemaître, Y.Eeckhout, E.F.Meyer.

ABSTRACT

The matrix metalloproteinases are crucial in the physiological and pathological degradation of the mammalian extracellular matrix, including breast tumours, and osteoarthritic cartilage. These enzymes are classified according to their matrix substrate specificity. Collagenase-3 (MMP-13) is a member of this family and preferentially cleaves type II collagen, cartilage, fibronectin and aggrecan. Collagenase-3 is normally expressed in hypertrophic chondrocytes, periosteal cells, and osteoblasts during bone development. The structure of the catalytic domain of recombinant mouse collagenase-3, complexed to the hydroxamate inhibitor (RS-113456), is reported at 2.0 A resolution. Molecular replacement and weak phasing information from a single derivative determined the structure. Neither molecular replacement nor derivative methods had a sufficient radius of convergence to yield a refinable structure. The structure illuminates the atomic zinc ion interactions with functional groups in the active site, emphasizing zinc ligation and the very voluminous hydrophobic P1' group for the inhibitor potency. The structure provides insight into the specificity of this enzyme, facilitating design of specific inhibitors to target various diseases.

Selected figure(s)

Figure 1.
Figure 1. Ribbon diagram of collagenase-3 with the catalytic and structural zinc atoms (blue spheres), the structural calcium atoms (red spheres) and the bound RS-113456 inhibitor. Figure created with SPOCK [Christopher 1998] and rendered with Raster-3D [Bacon and Anderson 1988 and Merritt and Murphy 1994].

Figure 3.
Figure 3. Stereo view of active site region with the catalytic zinc atom (blue sphere), ligating histidine residues and bound inhibitor. Omit map contoured at 2.0 s. Figure created with SPOCK.

The above figures are reprinted by permission from Elsevier: J Mol Biol (1999, 292, 837-844) copyright 1999.

Figures were selected by an automated process.