 |
PDBsum entry 2srt
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Hydrolase/hydrolase inhibitor
|
PDB id
|
|
|
|
2srt
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
Contents |
 |
|
|
|
|
|
|
|
|
|
|
|
|
* Residue conservation analysis
|
|
|
|
|
|
|
|
|
|
|
Enzyme class:
|
|
E.C.3.4.24.17
- stromelysin 1.
|
|
|
|
|
|
|
Reaction:
|
|
Preferential cleavage where P1', P2' and P3' are hydrophobic residues.
|
|
|
|
|
|
Cofactor:
|
|
Ca(2+); Zn(2+)
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
| |
|
|
Nat Struct Biol
1:111-118
(1994)
|
|
PubMed id:
|
|
|
|
|
|
| |
|
The NMR structure of the inhibited catalytic domain of human stromelysin-1.
|
|
P.R.Gooley,
J.F.O'Connell,
A.I.Marcy,
G.C.Cuca,
S.P.Salowe,
B.L.Bush,
J.D.Hermes,
C.K.Esser,
W.K.Hagmann,
J.P.Springer.
|
|
|
|
|
| |
ABSTRACT
|
|
|
|
| |
|
|
The three-dimensional structure of the catalytic domain of stromelysin-1
complexed with an N-carboxyl alkyl inhibitor has been determined by NMR methods.
The global fold consists of three helices, a five stranded beta-sheet and a
methionine located in a turn near the catalytic histidines, classifying
stromelysin-1 as a metzincin. Stromelysin-1 is unique in having two independent
zinc binding sites: a catalytic site and a structural site. The inhibitor binds
in an extended conformation. The S1' subsite is a deep hydrophobic pocket,
whereas S2' appears shallow and S3' open.
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
 |
 |
|
Literature references that cite this PDB file's key reference
|
|
|
| |
PubMed id
|
|
Reference
|
|
|
|
|
|
H.P.Shin,
J.I.Lee,
J.H.Jung,
S.V.Yim,
H.J.Kim,
J.M.Cha,
J.B.Park,
K.R.Joo,
J.S.Hwang,
and
B.K.Jang
(2008).
Matrix metalloproteinase (MMP)-3 polymorphism in patients with HBV related chronic liver disease.
|
| |
Dig Dis Sci,
53,
823-829.
|
|
|
|
|
|
|
L.R.Pal,
and
C.Guda
(2006).
Tracing the origin of functional and conserved domains in the human proteome: implications for protein evolution at the modular level.
|
| |
BMC Evol Biol,
6,
91.
|
|
|
|
|
|
|
H.I.Park,
Y.Jin,
D.R.Hurst,
C.A.Monroe,
S.Lee,
M.A.Schwartz,
and
Q.X.Sang
(2003).
The intermediate S1' pocket of the endometase/matrilysin-2 active site revealed by enzyme inhibition kinetic studies, protein sequence analyses, and homology modeling.
|
| |
J Biol Chem,
278,
51646-51653.
|
|
|
|
|
|
|
W.Bode,
and
K.Maskos
(2003).
Structural basis of the matrix metalloproteinases and their physiological inhibitors, the tissue inhibitors of metalloproteinases.
|
| |
Biol Chem,
384,
863-872.
|
|
|
|
|
|
|
Z.R.Wasserman,
J.J.Duan,
M.E.Voss,
C.B.Xue,
R.J.Cherney,
D.J.Nelson,
K.D.Hardman,
and
C.P.Decicco
(2003).
Identification of a selectivity determinant for inhibition of tumor necrosis factor-alpha converting enzyme by comparative modeling.
|
| |
Chem Biol,
10,
215-223.
|
|
|
|
|
|
|
E.Morgunova,
A.Tuuttila,
U.Bergmann,
and
K.Tryggvason
(2002).
Structural insight into the complex formation of latent matrix metalloproteinase 2 with tissue inhibitor of metalloproteinase 2.
|
| |
Proc Natl Acad Sci U S A,
99,
7414-7419.
|
|
|
PDB code:
|
|
|
|
|
|
|
|
K.Kaur,
K.Zhu,
M.S.Whittemore,
R.L.Petersen,
A.Lichte,
H.Tschesche,
and
T.Pourmotabbed
(2002).
Identification of the active site of gelatinase B as the structural element sufficient for converting a protein to a metalloprotease.
|
| |
Biochemistry,
41,
4789-4797.
|
|
|
|
|
|
|
B.Arza,
M.De Maeyer,
J.Félez,
D.Collen,
and
H.R.Lijnen
(2001).
Critical role of glutamic acid 202 in the enzymatic activity of stromelysin-1 (MMP-3).
|
| |
Eur J Biochem,
268,
826-831.
|
|
|
|
|
|
|
V.Knäuper,
M.L.Patterson,
F.X.Gomis-Rüth,
B.Smith,
A.Lyons,
A.J.Docherty,
and
G.Murphy
(2001).
The role of exon 5 in fibroblast collagenase (MMP-1) substrate specificity and inhibitor selectivity.
|
| |
Eur J Biochem,
268,
1888-1896.
|
|
|
|
|
|
|
D.E.Brodersen,
J.Nyborg,
and
M.Kjeldgaard
(1999).
Zinc-binding site of an S100 protein revealed. Two crystal structures of Ca2+-bound human psoriasin (S100A7) in the Zn2+-loaded and Zn2+-free states.
|
| |
Biochemistry,
38,
1695-1704.
|
|
|
PDB codes:
|
|
|
|
|
|
|
|
E.Morgunova,
A.Tuuttila,
U.Bergmann,
M.Isupov,
Y.Lindqvist,
G.Schneider,
and
K.Tryggvason
(1999).
Structure of human pro-matrix metalloproteinase-2: activation mechanism revealed.
|
| |
Science,
284,
1667-1670.
|
|
|
PDB code:
|
|
|
|
|
|
|
|
F.J.Moy,
P.K.Chanda,
J.M.Chen,
S.Cosmi,
W.Edris,
J.S.Skotnicki,
J.Wilhelm,
and
R.Powers
(1999).
NMR solution structure of the catalytic fragment of human fibroblast collagenase complexed with a sulfonamide derivative of a hydroxamic acid compound.
|
| |
Biochemistry,
38,
7085-7096.
|
|
|
PDB codes:
|
|
|
|
|
|
|
|
K.Briknarová,
A.Grishaev,
L.Bányai,
H.Tordai,
L.Patthy,
and
M.Llinás
(1999).
The second type II module from human matrix metalloproteinase 2: structure, function and dynamics.
|
| |
Structure,
7,
1235-1245.
|
|
|
PDB code:
|
|
|
|
|
|
|
|
L.L.Johnson,
D.A.Bornemeier,
J.A.Janowicz,
J.Chen,
A.G.Pavlovsky,
and
D.F.Ortwine
(1999).
Effect of species differences on stromelysin-1 (MMP-3) inhibitor potency. An explanation of inhibitor selectivity using homology modeling and chimeric proteins.
|
| |
J Biol Chem,
274,
24881-24887.
|
|
|
|
|
|
|
T.Meinnel,
L.Patiny,
S.Ragusa,
and
S.Blanquet
(1999).
Design and synthesis of substrate analogue inhibitors of peptide deformylase.
|
| |
Biochemistry,
38,
4287-4295.
|
|
|
|
|
|
|
W.Bode,
C.Fernandez-Catalan,
F.Grams,
F.X.Gomis-Rüth,
H.Nagase,
H.Tschesche,
and
K.Maskos
(1999).
Insights into MMP-TIMP interactions.
|
| |
Ann N Y Acad Sci,
878,
73-91.
|
|
|
|
|
|
|
A.Becker,
I.Schlichting,
W.Kabsch,
S.Schultz,
and
A.F.Wagner
(1998).
Structure of peptide deformylase and identification of the substrate binding site.
|
| |
J Biol Chem,
273,
11413-11416.
|
|
|
PDB codes:
|
|
|
|
|
|
|
|
B.C.Finzel,
E.T.Baldwin,
G.L.Bryant,
G.F.Hess,
J.W.Wilks,
C.M.Trepod,
J.E.Mott,
V.P.Marshall,
G.L.Petzold,
R.A.Poorman,
T.J.O'Sullivan,
H.J.Schostarez,
and
M.A.Mitchell
(1998).
Structural characterizations of nonpeptidic thiadiazole inhibitors of matrix metalloproteinases reveal the basis for stromelysin selectivity.
|
| |
Protein Sci,
7,
2118-2126.
|
|
|
PDB codes:
|
|
|
|
|
|
|
|
B.J.Stockman,
D.J.Waldon,
J.A.Gates,
T.A.Scahill,
D.A.Kloosterman,
S.A.Mizsak,
E.J.Jacobsen,
K.L.Belonga,
M.A.Mitchell,
B.Mao,
J.D.Petke,
L.Goodman,
E.A.Powers,
S.R.Ledbetter,
P.S.Kaytes,
G.Vogeli,
V.P.Marshall,
G.L.Petzold,
and
R.A.Poorman
(1998).
Solution structures of stromelysin complexed to thiadiazole inhibitors.
|
| |
Protein Sci,
7,
2281-2286.
|
|
|
PDB code:
|
|
|
|
|
|
|
|
F.Ugwu,
B.Van Hoef,
A.Bini,
D.Collen,
and
H.R.Lijnen
(1998).
Proteolytic cleavage of urokinase-type plasminogen activator by stromelysin-1 (MMP-3).
|
| |
Biochemistry,
37,
7231-7236.
|
|
|
|
|
|
|
I.L.Alberts,
K.Nadassy,
and
S.J.Wodak
(1998).
Analysis of zinc binding sites in protein crystal structures.
|
| |
Protein Sci,
7,
1700-1716.
|
|
|
|
|
|
|
Y.C.Li,
X.Zhang,
R.Melton,
V.Ganu,
and
N.C.Gonnella
(1998).
Solution structure of the catalytic domain of human stromelysin-1 complexed to a potent, nonpeptidic inhibitor.
|
| |
Biochemistry,
37,
14048-14056.
|
|
|
PDB code:
|
|
|
|
|
|
|
|
J.C.Müller,
E.G.von Roedern,
F.Grams,
H.Nagase,
and
L.Moroder
(1997).
Non-peptidic cysteine derivatives as inhibitors of matrix metalloproteinases.
|
| |
Biol Chem,
378,
1475-1480.
|
|
|
|
|
|
|
M.Betz,
P.Huxley,
S.J.Davies,
Y.Mushtaq,
M.Pieper,
H.Tschesche,
W.Bode,
and
F.X.Gomis-Rüth
(1997).
1.8-A crystal structure of the catalytic domain of human neutrophil collagenase (matrix metalloproteinase-8) complexed with a peptidomimetic hydroxamate primed-side inhibitor with a distinct selectivity profile.
|
| |
Eur J Biochem,
247,
356-363.
|
|
|
PDB code:
|
|
|
|
|
|
|
|
D.R.Wetmore,
and
K.D.Hardman
(1996).
Roles of the propeptide and metal ions in the folding and stability of the catalytic domain of stromelysin (matrix metalloproteinase 3).
|
| |
Biochemistry,
35,
6549-6558.
|
|
|
|
|
|
|
Q.A.Sang,
and
D.A.Douglas
(1996).
Computational sequence analysis of matrix metalloproteinases.
|
| |
J Protein Chem,
15,
137-160.
|
|
|
|
|
|
|
R.A.Williamson,
D.Natalia,
C.K.Gee,
G.Murphy,
M.D.Carr,
and
R.B.Freedman
(1996).
Chemically and conformationally authentic active domain of human tissue inhibitor of metalloproteinases-2 refolded from bacterial inclusion bodies.
|
| |
Eur J Biochem,
241,
476-483.
|
|
|
|
|
|
|
V.Dhanaraj,
Q.Z.Ye,
L.L.Johnson,
D.J.Hupe,
D.F.Ortwine,
J.B.Dunbar,
J.R.Rubin,
A.Pavlovsky,
C.Humblet,
and
T.L.Blundell
(1996).
X-ray structure of a hydroxamate inhibitor complex of stromelysin catalytic domain and its comparison with members of the zinc metalloproteinase superfamily.
|
| |
Structure,
4,
375-386.
|
|
|
|
|
|
|
A.Beaumont,
M.J.O'Donohue,
N.Paredes,
N.Rousselet,
M.Assicot,
C.Bohuon,
M.C.Fournié-Zaluski,
and
B.P.Roques
(1995).
The role of histidine 231 in thermolysin-like enzymes. A site-directed mutagenesis study.
|
| |
J Biol Chem,
270,
16803-16808.
|
|
|
|
|
|
|
D.Soler,
T.Nomizu,
W.E.Brown,
Y.Shibata,
and
D.S.Auld
(1995).
Matrilysin: expression, purification, and characterization.
|
| |
J Protein Chem,
14,
511-520.
|
|
|
|
|
|
|
F.Grams,
P.Reinemer,
J.C.Powers,
T.Kleine,
M.Pieper,
H.Tschesche,
R.Huber,
and
W.Bode
(1995).
X-ray structures of human neutrophil collagenase complexed with peptide hydroxamate and peptide thiol inhibitors. Implications for substrate binding and rational drug design.
|
| |
Eur J Biochem,
228,
830-841.
|
|
|
PDB codes:
|
|
|
|
|
|
|
|
J.W.Becker,
A.I.Marcy,
L.L.Rokosz,
M.G.Axel,
J.J.Burbaum,
P.M.Fitzgerald,
P.M.Cameron,
C.K.Esser,
W.K.Hagmann,
and
J.D.Hermes
(1995).
Stromelysin-1: three-dimensional structure of the inhibited catalytic domain and of the C-truncated proenzyme.
|
| |
Protein Sci,
4,
1966-1976.
|
|
|
PDB codes:
|
|
|
|
|
|
|
|
N.C.Gonnella,
R.Bohacek,
X.Zhang,
I.Kolossváry,
C.G.Paris,
R.Melton,
C.Winter,
S.I.Hu,
and
V.Ganu
(1995).
Bioactive conformation of stromelysin inhibitors determined by transferred nuclear Overhauser effects.
|
| |
Proc Natl Acad Sci U S A,
92,
462-466.
|
|
|
|
|
|
|
S.R.Van Doren,
A.V.Kurochkin,
W.Hu,
Q.Z.Ye,
L.L.Johnson,
D.J.Hupe,
and
E.R.Zuiderweg
(1995).
Solution structure of the catalytic domain of human stromelysin complexed with a hydrophobic inhibitor.
|
| |
Protein Sci,
4,
2487-2498.
|
|
|
PDB codes:
|
|
|
|
|
|
|
|
T.Pourmotabbed,
J.A.Aelion,
D.Tyrrell,
K.A.Hasty,
C.H.Bu,
and
C.L.Mainardi
(1995).
Role of the conserved histidine and aspartic acid residues in activity and stabilization of human gelatinase B: an example of matrix metalloproteinases.
|
| |
J Protein Chem,
14,
527-535.
|
|
|
|
|
|
|
W.Stöcker,
and
W.Bode
(1995).
Structural features of a superfamily of zinc-endopeptidases: the metzincins.
|
| |
Curr Opin Struct Biol,
5,
383-390.
|
|
|
|
|
|
|
P.M.Colman
(1994).
Structure-based drug design.
|
| |
Curr Opin Struct Biol,
4,
868-874.
|
|
|
|
|
|
|
S.S.Twining
(1994).
Regulation of proteolytic activity in tissues.
|
| |
Crit Rev Biochem Mol Biol,
29,
315-383.
|
|
|
|
|
|
|
T.L.Blundell
(1994).
Metalloproteinase superfamilies and drug design.
|
| |
Nat Struct Biol,
1,
73-75.
|
|
|
|
|
|
The most recent references are shown first.
Citation data come partly from CiteXplore and partly
from an automated harvesting procedure. Note that this is likely to be
only a partial list as not all journals are covered by
either method. However, we are continually building up the citation data
so more and more references will be included with time.
Where a reference describes a PDB structure, the PDB
code is
shown on the right.
|
|
Links
