PDBsum entry 2clt

Hydrolase

PDB id: 2clt

Contents

Protein chain

367 a.a. *

Metals

_ZN ×4

_CA ×8

Waters ×198

* Residue conservation analysis

PDB id:

2clt

Name:

Hydrolase

Title:

Crystal structure of the active form (full-length) of human fibroblast collagenase.

Structure:

Interstitial collagenase. Chain: a, b. Synonym: matrix metalloproteinase - 1, mmp-1, fibroblast collagenase. Engineered: yes. Mutation: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 469008.

Resolution:

2.67Å R-factor: 0.223 R-free: 0.259

Authors:

S.Iyer,R.Visse,H.Nagase,K.R.Acharya

Key ref:

S.Iyer et al. (2006). Crystal structure of an active form of human MMP-1. J Mol Biol, 362, 78-88. PubMed id: 16890240 DOI: 10.1016/j.jmb.2006.06.079

Date:

29-Apr-06 Release date: 09-Aug-06

Protein chains

P03956  (MMP1_HUMAN) -  Interstitial collagenase from Homo sapiens

Seq: 469 a.a.

Struc: 367 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class: E.C.3.4.24.7 - interstitial collagenase.
• Reaction: Cleaves preferentially one bond in native collagen. Cleavage of the triple helix of collagen at about three-quarters of the length of the molecule from the N-terminus, at 775-Gly-|-Ile-776 in the alpha-1(I) chain. Cleaves synthetic substrates and alpha-macroglobulins at bonds where P1' is a hydrophobic residue.
• Cofactor: Zn(2+)

DOI no: 10.1016/j.jmb.2006.06.079

J Mol Biol 362:78-88 (2006)

PubMed id: 16890240

Crystal structure of an active form of human MMP-1.

S.Iyer, R.Visse, H.Nagase, K.R.Acharya.

ABSTRACT

The extracellular matrix is a dynamic environment that constantly undergoes remodelling and degradation during vital physiological processes such as angiogenesis, wound healing, and development. Unbalanced extracellular matrix breakdown is associated with many diseases such as arthritis, cancer and fibrosis. Interstitial collagen is degraded by matrix metalloproteinases with collagenolytic activity by MMP-1, MMP-8 and MMP-13, collectively known as the collagenases. Matrix metalloproteinase 1 (MMP-1) plays a pivotal role in degradation of interstitial collagen types I, II, and III. Here, we report the crystal structure of the active form of human MMP-1 at 2.67 A resolution. This is the first MMP-1 structure that is free of inhibitor and a water molecule essential for peptide hydrolysis is observed coordinated with the active site zinc. Comparing this structure with the human proMMP-1 shows significant structural differences, mainly in the relative orientation of the hemopexin domain, between the pro form and active form of the human enzyme.

Selected figure(s)

Figure 3.

Figure 4.
Figure 4. Comparison of the hydrogen-bonding interactions within the linker region. (a) Superposition of active MMP-1 (pink) and procollagenase-1 (green) to highlight the conformational similarity of the linker region in the two structures. (b) Stereo view of the linker region in active MMP-1 showing the hydrogen-bonding interactions between the residues. (c) Stereo view of the linker region in procollagenase-1 showing the hydrogen bonds within the region.

The above figures are reprinted from an Open Access publication published by Elsevier: J Mol Biol (2006, 362, 78-88) copyright 2006.

Figures were selected by an automated process.