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PDBsum entry 5ezx
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Hydrolase/inhibitor
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PDB id
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5ezx
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PDB id:
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| Name: |
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Hydrolase/inhibitor
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Title:
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Crystal structure of bace-1 in complex with {(1r,2r)-2-[(r)-2-amino-4- (4-difluoromethoxy-phenyl)-4,5-dihydro-oxazol-4-yl]-cyclopropyl}-(5- chloro-pyridin-3-yl)-methanone
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Structure:
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Beta-secretase 1. Chain: a. Fragment: unp residues 57-446. Synonym: aspartyl protease 2,asp 2,beta-site amyloid precursor protein cleaving enzyme 1,beta-site app cleaving enzyme 1,memapsin-2, membrane-associated aspartic protease 2. Engineered: yes. Mutation: yes
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Gene: bace1, bace, kiaa1149. Expressed in: escherichia coli. Expression_system_taxid: 562
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Resolution:
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1.90Å
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R-factor:
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0.210
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R-free:
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0.236
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Authors:
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D.Banner,J.Benz,M.Stihle,A.Kuglstatter
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Key ref:
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B.Kuhn
et al.
(2016).
A Real-World Perspective on Molecular Design.
J Med Chem,
59,
4087-4102.
PubMed id:
DOI:
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Date:
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27-Nov-15
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Release date:
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24-Feb-16
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PROCHECK
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Headers
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References
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P56817
(BACE1_HUMAN) -
Beta-secretase 1 from Homo sapiens
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Seq:
Struc:
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501 a.a.
374 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 1 residue position (black
cross)
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DOI no:
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J Med Chem
59:4087-4102
(2016)
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PubMed id:
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A Real-World Perspective on Molecular Design.
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B.Kuhn,
W.Guba,
J.Hert,
D.Banner,
C.Bissantz,
S.Ceccarelli,
W.Haap,
M.Körner,
A.Kuglstatter,
C.Lerner,
P.Mattei,
W.Neidhart,
E.Pinard,
M.G.Rudolph,
T.Schulz-Gasch,
T.Woltering,
M.Stahl.
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ABSTRACT
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We present a series of small molecule drug discovery case studies where
computational methods were prospectively employed to impact Roche research
projects, with the aim of highlighting those methods that provide real added
value. Our brief accounts encompass a broad range of methods and techniques
applied to a variety of enzymes and receptors. Most of these are based on
judicious application of knowledge about molecular conformations and
interactions: filling of lipophilic pockets to gain affinity or selectivity,
addition of polar substituents, scaffold hopping, transfer of SAR, conformation
analysis, and molecular overlays. A case study of sequence-driven focused
screening is presented to illustrate how appropriate preprocessing of
information enables effective exploitation of prior knowledge. We conclude that
qualitative statements enabling chemists to focus on promising regions of
chemical space are often more impactful than quantitative prediction.
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Links
