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PDBsum entry 1zxc
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Contents |
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* Residue conservation analysis
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PDB id:
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Hydrolase
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Title:
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Crystal structure of catalytic domain of tnf-alpha converting enzyme (tace) with inhibitor
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Structure:
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Adam 17. Chain: a, b. Synonym: a disintegrin and metalloproteinase domain 17, tnf-alpha converting enzyme, tnf-alpha convertase, snake venom-like protease, cd156b antigen. Engineered: yes. Mutation: yes
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Gene: adam17, csvp, tace. Expressed in: escherichia coli. Expression_system_taxid: 562
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Resolution:
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2.28Å
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R-factor:
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0.216
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R-free:
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0.285
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Authors:
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J.I.Levin,J.M.Chen,L.M.Laakso,M.Du,J.Schmid,W.Xu,T.Cummons,J.Xu, Y.Zhang,G.Jin,R.Cowling,D.Barone,J.S.Skotnicki
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Key ref:
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J.I.Levin
et al.
(2005).
Acetylenic TACE inhibitors. Part 2: SAR of six-membered cyclic sulfonamide hydroxamates.
Bioorg Med Chem Lett,
15,
4345-4349.
PubMed id:
DOI:
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Date:
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07-Jun-05
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Release date:
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27-Sep-05
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PROCHECK
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Headers
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References
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P78536
(ADA17_HUMAN) -
Disintegrin and metalloproteinase domain-containing protein 17 from Homo sapiens
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Seq:
Struc:
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824 a.a.
259 a.a.*
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Key: |
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PfamA domain |
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Secondary structure |
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CATH domain |
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*
PDB and UniProt seqs differ
at 2 residue positions (black
crosses)
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Enzyme class:
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E.C.3.4.24.86
- Adam 17 endopeptidase.
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Cofactor:
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Zn(2+)
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DOI no:
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Bioorg Med Chem Lett
15:4345-4349
(2005)
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PubMed id:
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Acetylenic TACE inhibitors. Part 2: SAR of six-membered cyclic sulfonamide hydroxamates.
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J.I.Levin,
J.M.Chen,
L.M.Laakso,
M.Du,
X.Du,
A.M.Venkatesan,
V.Sandanayaka,
A.Zask,
J.Xu,
W.Xu,
Y.Zhang,
J.S.Skotnicki.
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ABSTRACT
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The SAR of a series of potent sulfonamide hydroxamate TACE inhibitors bearing a
butynyloxy P1' group was explored. In particular, compound 5k has excellent in
vitro potency against TACE enzyme and in cells, and oral activity in an in vivo
model of TNF-alpha production and a collagen-induced arthritis model.
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Literature references that cite this PDB file's key reference
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PubMed id
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Reference
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C.Dai,
D.Li,
J.Popovici-Muller,
L.Zhao,
V.M.Girijavallabhan,
K.E.Rosner,
B.J.Lavey,
R.Rizvi,
B.B.Shankar,
M.K.Wong,
Z.Guo,
P.Orth,
C.O.Strickland,
J.Sun,
X.Niu,
S.Chen,
J.A.Kozlowski,
D.J.Lundell,
J.J.Piwinski,
N.Y.Shih,
and
M.A.Siddiqui
(2011).
2-(2-Aminothiazol-4-yl)pyrrolidine-based tartrate diamides as potent, selective and orally bioavailable TACE inhibitors.
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Bioorg Med Chem Lett,
21,
3172-3176.
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PDB code:
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A.Trabocchi,
I.Stefanini,
M.Morvillo,
L.Ciofi,
D.Cavalieri,
and
A.Guarna
(2010).
Chemical genetics approach to identify new small molecule modulators of cell growth by phenotypic screening of Saccharomyces cerevisiae strains with a library of morpholine-derived compounds.
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Org Biomol Chem,
8,
5552-5557.
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F.Sladojevich,
A.Guarna,
and
A.Trabocchi
(2010).
Evaluation of stereochemically dense morpholine-based scaffolds as proline surrogates in beta-turn peptides.
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Org Biomol Chem,
8,
916-924.
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M.S.Bahia,
and
O.Silakari
(2010).
Tumor necrosis factor alpha converting enzyme: an encouraging target for various inflammatory disorders.
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Chem Biol Drug Des,
75,
415-443.
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C.Lalli,
A.Trabocchi,
F.Sladojevich,
G.Menchi,
and
A.Guarna
(2009).
Diversity-oriented synthesis of morpholine-containing molecular scaffolds.
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Chemistry,
15,
7871-7875.
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J.F.Fisher,
and
S.Mobashery
(2006).
Recent advances in MMP inhibitor design.
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Cancer Metastasis Rev,
25,
115-136.
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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.
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Links
