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PDBsum entry 3cib
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protein ligands Protein-protein interface(s) links
Hydrolase PDB id
3cib

 

 

 

 

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Contents
Protein chains
390 a.a. *
Ligands
314 ×2
TAR ×2
Waters ×966
* Residue conservation analysis
PDB id:
3cib
Name: Hydrolase
Title: Structure of bace bound to sch727596
Structure: Beta-secretase 1. Chain: a, b. 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
Source: Homo sapiens. Human. Gene: bace1, bace. Expressed in: escherichia coli.
Resolution:
1.72Å     R-factor:   0.188     R-free:   0.216
Authors: C.Strickland,J.Cumming
Key ref: J.N.Cumming et al. (2008). Rational design of novel, potent piperazinone and imidazolidinone BACE1 inhibitors. Bioorg Med Chem Lett, 18, 3236-3241. PubMed id: 18468890
Date:
11-Mar-08     Release date:   10-Jun-08    
PROCHECK
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 Headers
 References

Protein chains
Pfam   ArchSchema ?
P56817  (BACE1_HUMAN) -  Beta-secretase 1 from Homo sapiens
Seq:
Struc: 		501 a.a.
390 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.3.4.23.46  - memapsin 2.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

 

 
Bioorg Med Chem Lett 18:3236-3241 (2008)
PubMed id: 18468890  
 
 
Rational design of novel, potent piperazinone and imidazolidinone BACE1 inhibitors.
J.N.Cumming, T.X.Le, S.Babu, C.Carroll, X.Chen, L.Favreau, P.Gaspari, T.Guo, D.W.Hobbs, Y.Huang, U.Iserloh, M.E.Kennedy, R.Kuvelkar, G.Li, J.Lowrie, N.A.McHugh, L.Ozgur, J.Pan, E.M.Parker, K.Saionz, A.W.Stamford, C.Strickland, D.Tadesse, J.Voigt, L.Wang, Y.Wu, L.Zhang, Q.Zhang.
 
  ABSTRACT  
 
Guided by structure-based design, we synthesized two novel series of potent inhibitors of BACE1 and generated extensive SAR around both the prime and non-prime side binding pockets. The key feature of both series is a cyclic amine motif specifically crafted to achieve interactions with both the flap and with the S2' pocket.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
19330459 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.
  Mol Divers, 14, 39-49.  
19443265 G.E.de Kloe, D.Bailey, R.Leurs, and I.J.de Esch (2009).
Transforming fragments into candidates: small becomes big in medicinal chemistry.
  Drug Discov Today, 14, 630-646.  
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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