PDBsum entry: 1fm1

Hydrolase

PDB id: 1fm1

Contents

Protein chain

158 a.a. *

Ligands

WAY

Metals

_ZN ×2

_CA

* Residue conservation analysis

PDB id:

1fm1

Name:

Hydrolase

Title:

Solution structure of the catalytic fragment of human collagenase-3 (mmp-13) complexed with a hydroxamic acid inhibitor

Structure:

Collagenase-3. Chain: a. Fragment: catalytic fragment. Synonym: mmp-13. Engineered: yes. Other_details: hydroxamic acid inhibitor complex

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562.

NMR struc:

30 models

Authors:

F.J.Moy,P.K.Chanda,J.M.Chen,S.Cosmi,W.Edris,J.I.Levin, R.Powers

Key ref:

F.J.Moy et al. (2000). High-resolution solution structure of the catalytic fragment of human collagenase-3 (MMP-13) complexed with a hydroxamic acid inhibitor. J Mol Biol, 302, 671-689. PubMed id: 10986126 DOI: 10.1006/jmbi.2000.4082

Date:

15-Aug-00 Release date: 15-Aug-01

Protein chain

P45452  (MMP13_HUMAN) -  Collagenase 3

Seq: 471 a.a.

Struc: 158 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.2000.4082

J Mol Biol 302:671-689 (2000)

PubMed id: 10986126

High-resolution solution structure of the catalytic fragment of human collagenase-3 (MMP-13) complexed with a hydroxamic acid inhibitor.

F.J.Moy, P.K.Chanda, J.M.Chen, S.Cosmi, W.Edris, J.I.Levin, R.Powers.

ABSTRACT

The high-resolution solution structure of the catalytic fragment of human collagenase-3 (MMP-13) complexed with a sulfonamide derivative of a hydroxamic acid compound (WAY-151693) has been determined by multidimensional heteronuclear NMR. A total of 30 structures were calculated for residues 7-164 by means of hybrid distance geometry-simulated annealing using a total of 3280 experimental NMR restraints. The atomic rms distribution about the mean coordinate positions for the 30 structures is 0.43(+/-0.05) A for the backbone atoms, 0.80(+/-0.09) A for all atoms, and 0.47(+/-0.04) A for all atoms excluding disordered side-chains. The overall structure of MMP-13 is composed of a beta-sheet consisting of five beta-strands in a mixed parallel and anti-parallel arrangement and three alpha-helices where its overall fold is consistent with previously solved MMP structures. A comparison of the NMR structure of MMP-13 with the published 1.6 A resolution X-ray structure indicates that the major differences between the structures is associated with loop dynamics and crystal-packing interactions. The side-chains of some active-site residues for the NMR and X-ray structures of MMP-13 adopt distinct conformations. This is attributed to the presence of unique inhibitors in the two structures that encounter distinct interactions with MMP-13. The major structural difference observed between the MMP-13 and MMP-1 NMR structures is the relative size and shape of the S1' pocket where this pocket is significantly longer for MMP-13, nearly reaching the surface of the protein. Additionally, MMP-1 and MMP-13 exhibit different dynamic properties for the active-site loop and the structural Zn-binding region. The inhibitor WAY-151693 is well defined in the MMP-13 active-site based on a total of 52 distance restraints. The binding motif of WAY-151693 in the MMP-13 complex is consistent with our previously reported MMP-1:CGS-27023A NMR structure and is similar to the MMP-13: RS-130830 X-ray structure.

Selected figure(s)

Figure 1.
Figure 1. Illustration of the sulfonamide derivative of the hydroxamic acid inhibitor (WAY-151693) with the corresponding proton labels.

Figure 2.
Figure 2. Cross-eyed stereoview of (a) the MMP-13 bound conformation of WAY-151693 and (b) the MMP-1 bound conformation of CGS-27023A.

The above figures are reprinted by permission from Elsevier: J Mol Biol (2000, 302, 671-689) copyright 2000.

Figures were selected by an automated process.