 |
PDBsum entry 1fbl
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Metalloprotease
|
PDB id
|
|
|
|
1fbl
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
References listed in PDB file
|
|
|
Key reference
|
|
|
Title
|
|
Structure of full-Length porcine synovial collagenase reveals a c-Terminal domain containing a calcium-Linked, Four-Bladed beta-Propeller.
|
|
|
Authors
|
|
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.
|
|
|
Ref.
|
|
Structure, 1995,
3,
541-549.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
Note In the PDB file this reference is
annotated as "TO BE PUBLISHED".
The citation details given above were identified by an automated
search of PubMed on title and author
names, giving a
percentage match of
93%.
|
|
|
|
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.
|
|
|
|
|
|
|
|
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.
|
|
|
Secondary reference #1
|
|
|
Title
|
|
Crystallization and preliminary X-Ray analysis of porcine synovial collagenase.
|
|
|
Authors
|
|
L.F.Lloyd,
T.Skarzyński,
A.J.Wonacott,
T.E.Cawston,
I.M.Clark,
C.J.Mannix,
G.P.Harper.
|
|
|
Ref.
|
|
J Mol Biol, 1989,
210,
237-238.
|
|
|
PubMed id
|
|
|
|
|
|
|
|
|
|
|
|
|
