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PDBsum entry 3f7h
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Contents |
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* Residue conservation analysis
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PDB id:
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Apoptosis
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Title:
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Structure of an ml-iap/xiap chimera bound to a peptidomimetic
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Structure:
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Baculoviral iap repeat-containing protein 7. Chain: a, b. Fragment: ml-iap residues 63-172. Synonym: kidney inhibitor of apoptosis protein, kiap, melanoma inhibitor of apoptosis protein, ml-iap, livin, ring finger protein 50. Engineered: yes. Mutation: yes
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Gene: birc7, kiap, livin, mliap, rnf50, unq5800/pro19607/pro21344. Expressed in: escherichia coli. Expression_system_taxid: 562.
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Resolution:
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1.80Å
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R-factor:
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0.150
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R-free:
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0.175
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Authors:
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M.C.Franklin,W.J.Fairbrother,F.Cohen
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Key ref:
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F.Cohen
et al.
(2009).
Orally bioavailable antagonists of inhibitor of apoptosis proteins based on an azabicyclooctane scaffold.
J Med Chem,
52,
1723-1730.
PubMed id:
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Date:
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09-Nov-08
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Release date:
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17-Mar-09
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PROCHECK
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Headers
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References
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Q96CA5
(BIRC7_HUMAN) -
Baculoviral IAP repeat-containing protein 7 from Homo sapiens
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Seq:
Struc:
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298 a.a.
90 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 9 residue positions (black
crosses)
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Enzyme class:
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E.C.2.3.2.27
- RING-type E3 ubiquitin transferase.
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Reaction:
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S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N6- ubiquitinyl-[acceptor protein]-L-lysine
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J Med Chem
52:1723-1730
(2009)
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PubMed id:
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Orally bioavailable antagonists of inhibitor of apoptosis proteins based on an azabicyclooctane scaffold.
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F.Cohen,
B.Alicke,
L.O.Elliott,
J.A.Flygare,
T.Goncharov,
S.F.Keteltas,
M.C.Franklin,
S.Frankovitz,
J.P.Stephan,
V.Tsui,
D.Vucic,
H.Wong,
W.J.Fairbrother.
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ABSTRACT
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A series of IAP antagonists based on an azabicyclooctane scaffold was designed
and synthesized. The most potent of these compounds, 14b, binds to the XIAP BIR3
domain, the BIR domain of ML-IAP, and the BIR3 domain of c-IAP1 with K(i) values
of 140, 38, and 33 nM, respectively. These compounds promote degradation of
c-IAP1, activate caspases, and lead to decreased viability of breast cancer
cells without affecting normal mammary epithelial cells. Finally, compound 14b
inhibits tumor growth when dosed orally in a breast cancer xenograft 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.Y.Yang,
H.Sun,
J.Chen,
Z.Nikolovska-Coleska,
and
S.Wang
(2009).
Importance of ligand reorganization free energy in protein-ligand binding-affinity prediction.
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J Am Chem Soc,
131,
13709-13721.
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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.
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Links
