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PDBsum entry 4n1b
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Transcription/inhibitor
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PDB id
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4n1b
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PDB id:
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| Name: |
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Transcription/inhibitor
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Title:
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Structure of keap1 kelch domain with(1s,2r)-2-[(1s)-1-[(1-oxo-2,3- dihydro-1h-isoindol-2-yl)methyl]-1,2,3,4-tetrahydroisoquinoline-2- carbonyl]cyclohexane-1-carboxylic acid
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Structure:
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Kelch-like ech-associated protein 1. Chain: a, b, c. Fragment: elch domain, unp residues 321-611. Synonym: cytosolic inhibitor of nrf2, inrf2, kelch-like protein 19. Engineered: yes. Mutation: yes
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Gene: keap1, inrf2, kiaa0132, klhl19. Expressed in: escherichia coli. Expression_system_taxid: 562
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Resolution:
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2.55Å
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R-factor:
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0.246
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R-free:
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0.287
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Authors:
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M.A.Smith,S.Duclos,E.Beaumont,J.Kwong,M.Brooks,J.Barker,E.Jnoff, F.Brookfield,J.P.Courade,O.Barker,T.Fryatt,C.Albrecht,S.Bromidge
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Key ref:
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E.Jnoff
et al.
(2014).
Binding mode and structure-activity relationships around direct inhibitors of the Nrf2-Keap1 complex.
Chemmedchem,
9,
699-705.
PubMed id:
DOI:
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Date:
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03-Oct-13
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Release date:
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19-Feb-14
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PROCHECK
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Headers
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References
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Q14145
(KEAP1_HUMAN) -
Kelch-like ECH-associated protein 1 from Homo sapiens
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Seq:
Struc:
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624 a.a.
286 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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DOI no:
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Chemmedchem
9:699-705
(2014)
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PubMed id:
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Binding mode and structure-activity relationships around direct inhibitors of the Nrf2-Keap1 complex.
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E.Jnoff,
C.Albrecht,
J.J.Barker,
O.Barker,
E.Beaumont,
S.Bromidge,
F.Brookfield,
M.Brooks,
C.Bubert,
T.Ceska,
V.Corden,
G.Dawson,
S.Duclos,
T.Fryatt,
C.Genicot,
E.Jigorel,
J.Kwong,
R.Maghames,
I.Mushi,
R.Pike,
Z.A.Sands,
M.A.Smith,
C.C.Stimson,
J.P.Courade.
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ABSTRACT
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An X-ray crystal structure of Kelch-like ECH-associated protein (Keap1)
co-crystallised with
(1S,2R)-2-[(1S)-1-[(1,3-dioxo-2,3-dihydro-1H-isoindol-2-yl)methyl]-1,2,3,4-tetrahydroisoquinolin-2-carbonyl]cyclohexane-1-carboxylic
acid (compound (S,R,S)-1 a) was obtained. This X-ray crystal structure
provides breakthrough experimental evidence for the true binding mode of the hit
compound (S,R,S)-1 a, as the ligand orientation was found to differ from that
of the initial docking model, which was available at the start of the project.
Crystallographic elucidation of this binding mode helped to focus and drive the
drug design process more effectively and efficiently.
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Links
