 |
|
|
|
|
|
 |
Contents |
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
* Residue conservation analysis
|
|
|
|
|
|
PDB id:
|
|
|
|
| Name: |
|
Hydrolase
|
|
|
Title:
|
|
X-ray structure of a novel matrix metalloproteinase inhibito complexed to stromelysin
|
|
Structure:
|
|
Stromelysin-1. Chain: a, b, c. Fragment: catalytic domain. Engineered: yes
|
|
Source:
|
|
Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562
|
|
Resolution:
|
|
|
2.00Å
|
R-factor:
|
0.244
|
R-free:
|
0.284
|
|
|
Authors:
|
|
P.Dunten,U.Kammlott,R.Crowther,W.Levin,L.H.Foley,P.Wang,R.Pa
|
|
Key ref:
|
|
P.Dunten
et al.
(2001).
X-ray structure of a novel matrix metalloproteinase inhibitor complexed to stromelysin.
Protein Sci,
10,
923-926.
PubMed id:
DOI:
|
|
|
Date:
|
|
|
27-Oct-00
|
Release date:
|
25-Apr-01
|
|
|
|
|
|
|
PROCHECK
|
|
|
|
|
|
Headers
|
|
|
|
References
|
|
|
|
|
|
|
|
|
|
|
|
P08254
(MMP3_HUMAN) -
Stromelysin-1
|
|
|
|
Seq:
Struc:
|
|
|
|
477 a.a.
168 a.a.
|
|
|
|
|
|
|
|
|
|
|
|
|
Key: |
 |
PfamA domain |
|
|
 |
Secondary structure |
|
 |
CATH domain |
|
|
|
|
|
|
|
|
|
|
|
|
|
Enzyme class:
|
|
E.C.3.4.24.17
- Stromelysin 1.
|
|
|
|
|
|
|
Reaction:
|
|
Preferential cleavage where P1', P2' and P3' are hydrophobic residues.
|
|
|
|
|
|
Cofactor:
|
|
Calcium; Zinc
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Gene Ontology (GO) functional annotation
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Cellular component
|
extracellular matrix
|
1 term
|
|
|
Biological process
|
proteolysis
|
1 term
|
|
|
Biochemical function
|
metallopeptidase activity
|
3 terms
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
| |
|
DOI no:
|
Protein Sci
10:923-926
(2001)
|
|
PubMed id:
|
|
|
|
|
|
| |
|
X-ray structure of a novel matrix metalloproteinase inhibitor complexed to stromelysin.
|
|
P.Dunten,
U.Kammlott,
R.Crowther,
W.Levin,
L.H.Foley,
P.Wang,
R.Palermo.
|
|
|
|
|
| |
ABSTRACT
|
|
|
|
| |
|
|
A new class of matrix metalloproteinase (MMP) inhibitors has been identified by
screening a collection of compounds against stromelysin. The inhibitors,
2,4,6-pyrimidine triones, have proven to be potent inhibitors of gelatinases A
and B. An X-ray crystal structure of one representative compound bound to the
catalytic domain of stromelysin shows that the compounds bind at the active site
and ligand the active-site zinc. The pyrimidine triones mimic substrates in
forming hydrogen bonds to key residues in the active site, and provide
opportunities for placing appropriately chosen groups into the S1' specificity
pocket of MMPS: A number of compounds have been synthesized and assayed against
stromelysin, and the variations in potency are explained in terms of the binding
mode revealed in the X-ray crystal structure.
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
 |
 |
|
Literature references that cite this PDB file's key reference
|
|
|
| |
PubMed id
|
|
Reference
|
|
|
|
|
|
M.Jagodzinska,
F.Huguenot,
G.Candiani,
and
M.Zanda
(2009).
Assessing the bioisosterism of the trifluoromethyl group with a protease probe.
|
| |
ChemMedChem, 4,
49-51.
|
|
|
|
|
|
|
A.Agrawal,
D.Romero-Perez,
J.A.Jacobsen,
F.J.Villarreal,
and
S.M.Cohen
(2008).
Zinc-binding groups modulate selective inhibition of MMPs.
|
| |
ChemMedChem, 3,
812-820.
|
|
|
|
|
|
|
J.F.Fisher,
and
S.Mobashery
(2006).
Recent advances in MMP inhibitor design.
|
| |
Cancer Metastasis Rev, 25,
115-136.
|
|
|
|
|
|
|
M.Xue,
N.T.Le,
and
C.J.Jackson
(2006).
Targeting matrix metalloproteases to improve cutaneous wound healing.
|
| |
Expert Opin Ther Targets, 10,
143-155.
|
|
|
|
|
|
|
M.Kontoyianni,
G.S.Sokol,
and
L.M.McClellan
(2005).
Evaluation of library ranking efficacy in virtual screening.
|
| |
J Comput Chem, 26,
11-22.
|
|
|
|
|
|
|
M.S.Celej,
G.G.Montich,
and
G.D.Fidelio
(2003).
Protein stability induced by ligand binding correlates with changes in protein flexibility.
|
| |
Protein Sci, 12,
1496-1506.
|
|
|
|
|
|
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.
|
|
Links
