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Hydrolase PDB id
1ndy
Jmol
Contents
Protein chain
349 a.a. *
Ligands
FR3
Metals
_ZN
Waters ×442
* Residue conservation analysis
PDB id:
1ndy
Name: Hydrolase
Title: Crystal structure of adenosine deaminase complexed with fr230513
Structure: Adenosine deaminase. Chain: a. Ec: 3.5.4.4
Source: Bos taurus. Cattle. Organism_taxid: 9913. Tissue: intestine
Resolution:
2.00Å     R-factor:   0.203     R-free:   0.210
Authors: T.Kinoshita
Key ref: T.Terasaka et al. (2004). A highly potent non-nucleoside adenosine deaminase inhibitor: efficient drug discovery by intentional lead hybridization. J Am Chem Soc, 126, 34-35. PubMed id: 14709046 DOI: 10.1021/ja040807h
Date:
09-Dec-02     Release date:   09-Dec-03    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P56658  (ADA_BOVIN) -  Adenosine deaminase
Seq:
Struc: 		363 a.a.
349 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 15 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: E.C.3.5.4.4  - Adenosine deaminase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Adenosine + H2O = inosine + NH3
Adenosine
 + H(2)O
 =
inosine
Bound ligand (Het Group name = FR3)
matches with 44.00% similarity 		+ NH(3)
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     cell surface   10 terms 
  Biological process     cell adhesion   42 terms 
  Biochemical function     hydrolase activity     5 terms  

 

 
    Added reference    
 
 
DOI no: 10.1021/ja040807h J Am Chem Soc 126:34-35 (2004)
PubMed id: 14709046  
 
 
A highly potent non-nucleoside adenosine deaminase inhibitor: efficient drug discovery by intentional lead hybridization.
T.Terasaka, T.Kinoshita, M.Kuno, I.Nakanishi.
 
  ABSTRACT  
 
We disclose herein the rapid discovery of the first highly potent (Ki = 7.7 nM) non-nucleoside adenosine deaminase (ADA) inhibitor based on the rational hybridization of two structurally distinct leads. Two micromolar inhibitors were discovered by a parallel rational design and random screening program, and individual crystal structures of bovine ADA in complexation with these inhibitors revealed several unknown binding sites and distinct binding modes. Using this information as the starting point, highly effective lead hybridization was achieved in only two structure-based drug design iterations. The conceptual approach illustrated by this example promises to be broadly useful in the search for new chemical entities and can contribute greatly to improve the overall efficiency and speed of drug discovery.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21457080 P.Zhan, and X.Liu (2011).
Novel HIV-1 non-nucleoside reverse transcriptase inhibitors: a patent review (2005 - 2010).
  Expert Opin Ther Pat, 21, 717-796.  
20923411 P.Burton, D.R.Adams, A.Abraham, R.W.Allcock, Z.Jiang, A.McCahill, J.Gilmour, J.McAbney, A.Kaupisch, N.M.Kane, G.S.Baillie, A.H.Baker, G.Milligan, M.D.Houslay, and J.C.Mountford (2010).
Erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA) blocks differentiation and maintains the expression of pluripotency markers in human embryonic stem cells.
  Biochem J, 432, 575-584.  
19845314 H.Fan, J.J.Irwin, B.M.Webb, G.Klebe, B.K.Shoichet, and A.Sali (2009).
Molecular docking screens using comparative models of proteins.
  J Chem Inf Model, 49, 2512-2527.  
18602399 E.T.Larson, W.Deng, B.E.Krumm, A.Napuli, N.Mueller, W.C.Van Voorhis, F.S.Buckner, E.Fan, A.Lauricella, G.DeTitta, J.Luft, F.Zucker, W.G.Hol, C.L.Verlinde, and E.A.Merritt (2008).
Structures of substrate- and inhibitor-bound adenosine deaminase from a human malaria parasite show a dramatic conformational change and shed light on drug selectivity.
  J Mol Biol, 381, 975-988.
PDB codes: 2pgf 2pgr 2qvn
17379970 T.Kinoshita (2007).
[Application and development of structure-based drug design using X-ray analysis]
  Nippon Yakurigaku Zasshi, 129, 186-190.  
17623865 V.Ramensky, A.Sobol, N.Zaitseva, A.Rubinov, and V.Zosimov (2007).
A novel approach to local similarity of protein binding sites substantially improves computational drug design results.
  Proteins, 69, 349-357.  
16856187 N.H.Elowe, R.Nutiu, A.Allali-Hassani, J.D.Cechetto, D.W.Hughes, Y.Li, and E.D.Brown (2006).
Small-molecule screening made simple for a difficult target with a signaling nucleic acid aptamer that reports on deaminase activity.
  Angew Chem Int Ed Engl, 45, 5648-5652.  
16245692 I.A.Il'icheva, I.u.P.Zarubin, P.A.Kostin, D.V.Mirgorodskiĭ, P.P.Purygin, and V.L.Florent'ev (2005).
[Theoretical study of the structure of adenosine deaminase complexes with adenosine analogues: I. Aza-, deaza- and isomeric azadeazaanalogues of adenosine]
  Bioorg Khim, 31, 488-502.  
  16511045 M.J.Ku, W.H.Lee, K.H.Nam, K.H.Rhee, K.S.Lee, E.E.Kim, M.H.Yu, and K.Y.Hwang (2005).
Crystallization and preliminary X-ray crystallographic analysis of the tRNA-specific adenosine deaminase from Streptococcus pyogenes.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 61, 375-377.  
16006182 S.P.Williams, L.F.Kuyper, and K.H.Pearce (2005).
Recent applications of protein crystallography and structure-guided drug design.
  Curr Opin Chem Biol, 9, 371-380.  
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. Where a reference describes a PDB structure, the PDB codes are shown on the right.