 |
PDBsum entry 1ck7
|
|
|
|
|
 |
Contents |
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
* Residue conservation analysis
|
|
|
|
|
References listed in PDB file
|
|
|
Key reference
|
|
|
Title
|
|
Structure of human pro-Matrix metalloproteinase-2: activation mechanism revealed.
|
|
|
Authors
|
|
E.Morgunova,
A.Tuuttila,
U.Bergmann,
M.Isupov,
Y.Lindqvist,
G.Schneider,
K.Tryggvason.
|
|
|
Ref.
|
|
Science, 1999,
284,
1667-1670.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
|
Abstract
|
|
|
Matrix metalloproteinases (MMPs) catalyze extracellular matrix degradation.
Control of their activity is a promising target for therapy of diseases
characterized by abnormal connective tissue turnover. MMPs are expressed as
latent proenzymes that are activated by proteolytic cleavage that triggers a
conformational change in the propeptide (cysteine switch). The structure of
proMMP-2 reveals how the propeptide shields the catalytic cleft and that the
cysteine switch may operate through cleavage of loops essential for propeptide
stability.
|
|
|
|
|
|
|
|
|
|
Figure 1.
Fig. 1. Structure of proMMP-2. The prodomain, catalytic domain,
fibronectin domains, and hemopexin domain are shown in red,
blue, green, and yellow, respectively. Zn^2+ ions are indicated
in red, and Ca^2+ ions are magenta (24). Asterisk indicates the
cleavage site for MT1-MMP.
|
|
Figure 3.
Fig. 3. Structure of fibronectin domains (24). (A) Stereoview
of the electron density map contoured around cis-Pro^236 (P236)
and the Cys^233 (C233) to Cys^259 (C259) disulfide bridge.
Sulfur atoms are yellow. (B) Ribbon representation showing the
secondary structure with the disulfide bridges. (C and D)
Molecular surface of the fibronectin domains show polar (green)
and hydrophobic (red) residues that bind to gelatin (19). The
orientation in (B) and (C) is the same, and the molecule in (D)
is rotated by 180°. F, Phe; L, Leu; W, Trp.
|
|
Figure 4.
Fig. 4. Interaction between propeptide and fibronectin
domains (24). (A) Stereoview of the propeptide residues in
contact with the hydrophobic pocket of the third fibronectin
domain. Hydrophobic residues from the fibronectin domain are
magenta and propeptide residues are yellow. Arg^368 (R368) and
Gly^367 (G367) (cyan) form hydrogen bonds with the propeptide
residues Asp^40 (D40) and Ile^35 (I35), respectively. (B)
Molecular surface of full-length proMMP-2. Colored surfaces
associated are with negatively charged (red) and positively
charged (blue) residues. Propeptide residues are represented as
a ball-and-stick model. Y, Tyr.
|
|
|
|
|
|
The above figures are
reprinted
by permission from the AAAs:
Science
(1999,
284,
1667-1670)
copyright 1999.
|
|
|
|
|
|
|
