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PDBsum entry 3dv1
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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 human beta-secretase in complex with nvp-arv999
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Structure:
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Beta-secretase 1. Chain: a, b, c. Fragment: catalytic domain: residues 48-447. Synonym: beta-site app cleaving enzyme 1, beta-site amyloid precursor protein cleaving enzyme 1, membrane-associated aspartic protease 2, memapsin-2, aspartyl protease 2, asp 2, asp2. Engineered: yes
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Source:
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Homo sapiens. Organism_taxid: 9606. Gene: bace1, bace. Expressed in: escherichia coli. Expression_system_taxid: 562.
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Resolution:
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2.10Å
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R-factor:
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0.223
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R-free:
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0.241
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Authors:
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J.-M.Rondeau
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Key ref:
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R.Machauer
et al.
(2009).
Macrocyclic peptidomimetic beta-secretase (BACE-1) inhibitors with activity in vivo.
Bioorg Med Chem Lett,
19,
1366-1370.
PubMed id:
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Date:
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18-Jul-08
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Release date:
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24-Feb-09
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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.
377 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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Bioorg Med Chem Lett
19:1366-1370
(2009)
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PubMed id:
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Macrocyclic peptidomimetic beta-secretase (BACE-1) inhibitors with activity in vivo.
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R.Machauer,
K.Laumen,
S.Veenstra,
J.M.Rondeau,
M.Tintelnot-Blomley,
C.Betschart,
A.L.Jaton,
S.Desrayaud,
M.Staufenbiel,
S.Rabe,
P.Paganetti,
U.Neumann.
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ABSTRACT
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The macrocyclic peptidic BACE-1 inhibitors 2a-c show moderate enzymatic and
cellular activity. By exchange of the hydroxyethylene- to
ethanolamine-transition state mimetic the peptidic character was reduced,
providing the highly potent and selective inhibitor 3. Variation of the P'
moiety resulted in the macrocyclic inhibitor 14. Both macrocycles show
inhibition of BACE-1 in the brain of APP51/16 transgenic mice, 3 (NB-544) after
intravenous and 14 (NB-533) after oral application.
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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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J.Alemán,
A.Núñez,
L.Marzo,
V.Marcos,
C.Alvarado,
and
J.L.García Ruano
(2010).
Asymmetric synthesis of 4-amino-4H-chromenes by organocatalytic oxa-Michael/aza-Baylis-Hillman tandem reactions.
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Chemistry,
16,
9453-9456.
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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
