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PDBsum entry 2ph6
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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 complexed with inhibitor
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Structure:
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Beta-secretase 1. Chain: a. Fragment: protease domain (residues 43-446). 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. Mutation: yes
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Gene: bace1, bace. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
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Resolution:
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2.00Å
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R-factor:
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0.195
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R-free:
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0.218
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Authors:
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S.Munshi
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Key ref:
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S.R.Lindsley
et al.
(2007).
Design, synthesis, and SAR of macrocyclic tertiary carbinamine BACE-1 inhibitors.
Bioorg Med Chem Lett,
17,
4057-4061.
PubMed id:
DOI:
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Date:
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10-Apr-07
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Release date:
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05-Jun-07
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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.
371 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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Bioorg Med Chem Lett
17:4057-4061
(2007)
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PubMed id:
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Design, synthesis, and SAR of macrocyclic tertiary carbinamine BACE-1 inhibitors.
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S.R.Lindsley,
K.P.Moore,
H.A.Rajapakse,
H.G.Selnick,
M.B.Young,
H.Zhu,
S.Munshi,
L.Kuo,
G.B.McGaughey,
D.Colussi,
M.C.Crouthamel,
M.T.Lai,
B.Pietrak,
E.A.Price,
S.Sankaranarayanan,
A.J.Simon,
G.R.Seabrook,
D.J.Hazuda,
N.T.Pudvah,
J.H.Hochman,
S.L.Graham,
J.P.Vacca,
P.G.Nantermet.
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ABSTRACT
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This Letter describes the design and synthesis of tertiary carbinamine
macrocyclic inhibitors of the beta-secretase (BACE-1) enzyme. These macrocyclic
inhibitors, some of which incorporate novel P2 substituents, display a 2- to
100-fold increase in potency relative to the previously described acyclic
analogs while affording greater stability.
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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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A.Pandey,
J.Mungalpara,
and
C.G.Mohan
(2010).
Comparative molecular field analysis and comparative molecular similarity indices analysis of hydroxyethylamine derivatives as selective human BACE-1 inhibitor.
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Mol Divers,
14,
39-49.
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P.Davies,
and
J.Koppel
(2009).
Mechanism-based treatments for Alzheimer's disease.
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Dialogues Clin Neurosci,
11,
159-169.
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A.K.Ghosh,
S.Gemma,
and
J.Tang
(2008).
beta-Secretase as a therapeutic target for Alzheimer's disease.
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Neurotherapeutics,
5,
399-408.
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A.Barazza,
M.Götz,
S.A.Cadamuro,
P.Goettig,
M.Willem,
H.Steuber,
T.Kohler,
A.Jestel,
P.Reinemer,
C.Renner,
W.Bode,
and
L.Moroder
(2007).
Macrocyclic statine-based inhibitors of BACE-1.
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Chembiochem,
8,
2078-2091.
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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
