PDBsum entry 1fbl

Metalloprotease

PDB id: 1fbl

Contents

Protein chain

367 a.a. *

Ligands

HTA

Metals

_CA ×4

_ZN ×2

Waters ×295

* Residue conservation analysis

PDB id:

1fbl

Name:

Metalloprotease

Title:

Structure of full-length porcine synovial collagenase (mmp1) reveals a c-terminal domain containing a calcium-linked, four-bladed beta- propeller

Structure:

Fibroblast (interstitial) collagenase (mmp-1). Chain: a. Engineered: yes

Source:

Sus scrofa. Pig. Organism_taxid: 9823. Expressed in: escherichia coli. Expression_system_taxid: 562

Biol. unit:

Dimer (from PQS)

Resolution:

2.50Å R-factor: 0.217

Authors:

J.Li,P.Brick,D.M.Blow

Key ref:

J.Li et al. (1995). Structure of full-length porcine synovial collagenase reveals a C-terminal domain containing a calcium-linked, four-bladed beta-propeller. Structure, 3, 541-549. PubMed id: 8590015 DOI: 10.1016/S0969-2126(01)00188-5

Date:

24-Apr-95 Release date: 29-Jan-96

Protein chain

P21692  (MMP1_PIG) -  Interstitial collagenase from Sus scrofa

Seq: 469 a.a.

Struc: 367 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: 10.1016/S0969-2126(01)00188-5

Structure 3:541-549 (1995)

PubMed id: 8590015

Structure of full-length porcine synovial collagenase reveals a C-terminal domain containing a calcium-linked, four-bladed beta-propeller.

J.Li, P.Brick, M.C.O'Hare, T.Skarzynski, L.F.Lloyd, V.A.Curry, I.M.Clark, H.F.Bigg, B.L.Hazleman, T.E.Cawston.

ABSTRACT

BACKGROUND: The collagenases are members of the family of zinc-dependent enzymes known as the matrix metalloproteinases (MMPs). They are the only proteinases that specifically cleave the collagen triple helix, and are important in a large number of physiological and pathological processes. Structures are known for the N-terminal catalytic' domain of collagenases MMP-1 and MMP-8 and of stromelysin (MMP-3). This catalytic domain alone, which comprises about 150 amino acids, has no activity against collagen. A second domain, of 200 amino acids, is homologous to haemopexin, a haem-binding glycoprotein. RESULTS: The crystal structure of full-length MMP-1 at 2.5 A resolution gives an R-factor of 21.7%. Two domains are connected by an exposed proline-rich linker of 17 amino acids, which is probably flexible and has no secondary structure. The catalytic domain resembles those previously observed, and contains three calcium-binding sites. The haemopexin-like domain contains four units of four-stranded antiparallel beta sheet stabilized on its fourfold axis by a cation, which is probably calcium. The domain constitutes a four-bladed beta-propeller structure in which the blades are scarcely twisted. CONCLUSIONS: The exposed linker accounts for the difficulty in purifying full-length collagenase. The C-terminal domain provides a structural model for haemopexin and its homologues. It controls the specificity of MMPs, affecting both substrate and inhibitor binding, although its role remains obscure. These structural results should aid the design of site-specific mutants which will reveal further details of the specificity mechanism.

Selected figure(s)

Figure 1.
Figure 1. Chemical structure of the CIC inhibitor. The material used was a racemic mixture of R- and S-configurations at the Cα of the leucine moiety. Figure 1. Chemical structure of the CIC inhibitor. The material used was a racemic mixture of R- and S-configurations at the Cα of the leucine moiety.

Figure 5.
Figure 5. Section of the electron-density map of the haemopexin-like domain comparable to the schematic diagram in Figure 4a. The map is contoured at 1σ and was calculated using coefficients (3F[o]–2F[c]) with phases obtained from the final model. Figure 5. Section of the electron-density map of the haemopexin-like domain comparable to the schematic diagram in [3]Figure 4a. The map is contoured at 1σ and was calculated using coefficients (3F[o]–2F[c]) with phases obtained from the final model.

The above figures are reprinted by permission from Cell Press: Structure (1995, 3, 541-549) copyright 1995.

Figures were selected by an automated process.