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PDBsum entry 3buf
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Hydrolase PDB id
3buf

 

 

 

 

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Contents
Protein chain
359 a.a. *
Ligands
AEG
Waters ×173
* Residue conservation analysis
PDB id:
3buf
Name: Hydrolase
Title: Bace-1 complexed with compound 2
Structure: Beta-secretase 1. Chain: a. Fragment: protease domain. 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
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562
Resolution:
2.30Å     R-factor:   0.204     R-free:   0.234
Authors: A.Kuglstatter,M.Hennig
Key ref: A.Kuglstatter et al. (2008). Tyramine fragment binding to BACE-1. Bioorg Med Chem Lett, 18, 1304-1307. PubMed id: 18226904
Date:
02-Jan-08     Release date:   11-Mar-08    
PROCHECK
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 Headers
 References

Protein chain
Pfam   ArchSchema ?
P56817  (BACE1_HUMAN) -  Beta-secretase 1 from Homo sapiens
Seq:
Struc: 		501 a.a.
359 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

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

 

 
Bioorg Med Chem Lett 18:1304-1307 (2008)
PubMed id: 18226904  
 
 
Tyramine fragment binding to BACE-1.
A.Kuglstatter, M.Stahl, J.U.Peters, W.Huber, M.Stihle, D.Schlatter, J.Benz, A.Ruf, D.Roth, T.Enderle, M.Hennig.
 
  ABSTRACT  
 
Fragment screening revealed that tyramine binds to the active site of the Alzheimer's disease drug target BACE-1. Hit expansion by selection of compounds from the Roche compound library identified tyramine derivatives with improved binding affinities as monitored by surface plasmon resonance. X-ray structures show that the amine of the tyramine fragment hydrogen-bonds to the catalytic water molecule. Structure-guided ligand design led to the synthesis of further low molecular weight compounds that are starting points for chemical leads.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21382336 T.Christopeit, G.Stenberg, T.Gossas, S.Nyström, V.Baraznenok, E.Lindström, and U.H.Danielson (2011).
A surface plasmon resonance-based biosensor with full-length BACE1 in a reconstituted membrane.
  Anal Biochem, 414, 14-22.  
20066707 A.Wetzel, G.Pratsch, R.Kolb, and M.R.Heinrich (2010).
Radical arylation of phenols, phenyl ethers, and furans.
  Chemistry, 16, 2547-2556.  
20471246 C.W.Murray, and T.L.Blundell (2010).
Structural biology in fragment-based drug design.
  Curr Opin Struct Biol, 20, 497-507.  
20017116 R.L.Rich, and D.G.Myszka (2010).
Grading the commercial optical biosensor literature-Class of 2008: 'The Mighty Binders'.
  J Mol Recognit, 23, 1.  
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.  
19247303 G.M.Keserü, and G.M.Makara (2009).
The influence of lead discovery strategies on the properties of drug candidates.
  Nat Rev Drug Discov, 8, 203-212.  
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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