PDBsum entry 1su3

Hydrolase

PDB id: 1su3

Contents

Protein chain

415 a.a. *

Ligands

SO4 ×5

EPE

Metals

_CA ×8

_CL ×2

_NA ×2

_ZN ×4

Waters ×372

* Residue conservation analysis

PDB id:

1su3

Name:

Hydrolase

Title:

X-ray structure of human prommp-1: new insights into collagenase action

Structure:

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

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: mmp1, clg. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.

Resolution:

2.20Å R-factor: 0.224 R-free: 0.252

Authors:

D.Jozic,G.Bourenkov,N.H.Lim,H.Nagase,W.Bode,K.Maskos,Structural Proteomics In Europe (Spine)

Key ref:

D.Jozic et al. (2005). X-ray structure of human proMMP-1: new insights into procollagenase activation and collagen binding. J Biol Chem, 280, 9578-9585. PubMed id: 15611040 DOI: 10.1074/jbc.M411084200

Date:

26-Mar-04 Release date: 21-Dec-04

Protein chains

P03956  (MMP1_HUMAN) -  Interstitial collagenase from Homo sapiens

Seq: 469 a.a.

Struc: 415 a.a.

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: 10.1074/jbc.M411084200

J Biol Chem 280:9578-9585 (2005)

PubMed id: 15611040

X-ray structure of human proMMP-1: new insights into procollagenase activation and collagen binding.

D.Jozic, G.Bourenkov, N.H.Lim, R.Visse, H.Nagase, W.Bode, K.Maskos.

ABSTRACT

Vertebrate collagenases, members of the matrix metalloproteinase (MMP) family, initiate interstitial fibrillar collagen breakdown. It is essential in many biological processes, and unbalanced collagenolysis is associated with diseases such as arthritis, cancer, atherosclerosis, aneurysm, and fibrosis. These metalloproteinases are secreted from the cell as inactive precursors, procollagenases (proMMPs). To gain insights into the structural basis of their activation mechanisms and collagen binding, we have crystallized recombinant human proMMP-1 and determined its structure to 2.2 A resolution. The catalytic metalloproteinase domain and the C-terminal hemopexin (Hpx) domain show the classical MMP-fold, but the structure has revealed new features in surface loops and domain interaction. The prodomain is formed by a three-helix bundle and gives insight into the stepwise activation mechanism of proMMP-1. The prodomain interacts with the Hpx domain, which affects the position of the Hpx domain relative to the catalytic domain. This interaction results in a "closed" configuration of proMMP-1 in contrast to the "open" configuration observed previously for the structure of active MMP-1. This is the first evidence of mobility of the Hpx domain in relation to the catalytic domain, providing an important clue toward the understanding of the collagenase-collagen interaction and subsequent collagenolysis.

Selected figure(s)

Figure 4.
FIG. 4. Interaction between the prodomain and the Hpx domain in proMMP-1. A, electron density figure of molecule A. The final 2.2 Å electron density is contoured at 1 , and the residues are shown as stick models in atom type. The figure was made with MAIN (24). B, interactions between the pro- and Hpx domains seen in molecule A of the asymmetric unit. Residues involved in the interaction between the prodomain (blue ribbon) and the Hpx domain (green ribbon) are shown as sticks and are labeled. Hydrogen bonds are shown as green dotted lines. The figure was made with the Swiss-PDB viewer (49).

Figure 6.
FIG. 6. The Hpx domain in pro- and active MMP-1 has a different conformation. A, both molecules of the asymmetric unit superimposed on their catalytic domains (dark pink, molecule A; green, molecule B). Note the difference in Hpx domain orientation. B, molecule B superimposed with active porcine MMP-1 (18), superimposed on the catalytic domain (cat). Molecule B is shown in green; active MMP-1 (Protein Data Bank accession code 1FBL [PDB] , porcine MMP-1) is shown in pink. C, same as B but rotated to show the difference of the catalytic-Hpx domain conformation in proMMP-1 and active MMP-1. The curved arrow indicates the relative movement between pro- and active MMP-1. The straight arrow indicates the cleft between the catalytic domain and the Hpx domain that is closed in proMMP-1 and open in active MMP-1. This figure was made with the Swiss-PDB viewer (49).

The above figures are reprinted by permission from the ASBMB: J Biol Chem (2005, 280, 9578-9585) copyright 2005.

Figures were selected by an automated process.