 |
PDBsum entry 2a8h
|
|
|
|
|
 |
Contents |
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
* Residue conservation analysis
|
|
|
|
|
|
PDB id:
|
|
|
|
| Name: |
|
Hydrolase
|
|
|
Title:
|
|
Crystal structure of catalytic domain of tace with thiomorpholine sulfonamide hydroxamate inhibitor
|
|
Structure:
|
|
Adam 17. Chain: a, b. Fragment: catalytic domain. Synonym: a disintegrin and metalloproteinase domain 17, tnf-alpha converting enzyme, tnf-alpha convertase, snake venom-like protease, cd156b antigen. Engineered: yes. Mutation: yes
|
|
Source:
|
|
Homo sapiens. Human. Organism_taxid: 9606. Gene: adam17, csvp, tace. Expressed in: escherichia coli. Expression_system_taxid: 562
|
|
Resolution:
|
|
|
2.30Å
|
R-factor:
|
0.218
|
R-free:
|
0.281
|
|
|
Authors:
|
|
J.I.Levin,J.M.Chen,L.M.Laakso,M.Du,J.Schmid,W.Xu,T.Cummons,J.Xu, G.Jin,D.Barone,J.S.Skotnicki
|
|
Key ref:
|
|
J.I.Levin
et al.
(2006).
Acetylenic TACE inhibitors. Part 3: Thiomorpholine sulfonamide hydroxamates.
Bioorg Med Chem Lett,
16,
1605-1609.
PubMed id:
DOI:
|
|
|
Date:
|
|
|
08-Jul-05
|
Release date:
|
07-Feb-06
|
|
|
|
|
|
|
PROCHECK
|
|
|
|
|
|
Headers
|
|
|
|
References
|
|
|
|
|
|
|
|
P78536
(ADA17_HUMAN) -
Disintegrin and metalloproteinase domain-containing protein 17 from Homo sapiens
|
|
|
|
Seq:
Struc:
|
|
|
|
824 a.a.
259 a.a.*
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Key: |
 |
PfamA domain |
|
|
 |
Secondary structure |
|
 |
CATH domain |
|
|
*
PDB and UniProt seqs differ
at 2 residue positions (black
crosses)
|
|
|
|
|
|
|
|
|
|
|
|
|
Enzyme class:
|
|
E.C.3.4.24.86
- Adam 17 endopeptidase.
|
|
|
|
|
|
|
Cofactor:
|
|
Zn(2+)
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
| |
|
DOI no:
|
Bioorg Med Chem Lett
16:1605-1609
(2006)
|
|
PubMed id:
|
|
|
|
|
|
| |
|
Acetylenic TACE inhibitors. Part 3: Thiomorpholine sulfonamide hydroxamates.
|
|
J.I.Levin,
J.M.Chen,
L.M.Laakso,
M.Du,
J.Schmid,
W.Xu,
T.Cummons,
J.Xu,
G.Jin,
D.Barone,
J.S.Skotnicki.
|
|
|
|
|
| |
ABSTRACT
|
|
|
|
| |
|
|
A series of thiomorpholine sulfonamide hydroxamate TACE inhibitors, all bearing
propargylic ether P1' groups, was explored. In particular, compound 5h has
excellent in vitro potency against isolated TACE enzyme and in cells, oral
activity in a model of TNF-alpha production and a collagen-induced arthritis
model, was selected as a clinical candidate for the treatment of RA.
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
 |
 |
|
Literature references that cite this PDB file's key reference
|
|
|
| |
PubMed id
|
|
Reference
|
|
|
|
|
|
M.S.Bahia,
and
O.Silakari
(2010).
Tumor necrosis factor alpha converting enzyme: an encouraging target for various inflammatory disorders.
|
| |
Chem Biol Drug Des,
75,
415-443.
|
|
|
|
|
|
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
