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PDBsum entry 2f64

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protein ligands Protein-protein interface(s) links
Transferase PDB id
2f64
Jmol
Contents
Protein chains
158 a.a. *
Ligands
SO4 ×2
12Q ×2
GOL ×2
Waters ×374
* Residue conservation analysis
PDB id:
2f64
Name: Transferase
Title: Crystal structure of nucleoside 2-deoxyribosyltransferase fr trypanosoma brucei at 1.6 a resolution with 1-methylquinoli one bound
Structure: Nucleoside 2-deoxyribosyltransferase. Chain: a, b. Engineered: yes
Source: Trypanosoma brucei. Organism_taxid: 5691. Gene: tb05.30h13.400. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Dimer (from PQS)
Resolution:
1.60Å     R-factor:   0.166     R-free:   0.187
Authors: J.Bosch,M.A.Robien,W.G.J.Hol,Structural Genomics Of Pathogen Protozoa Consortium (Sgpp)
Key ref: J.Bosch et al. (2006). Using fragment cocktail crystallography to assist inhibitor design of Trypanosoma brucei nucleoside 2-deoxyribosyltransferase. J Med Chem, 49, 5939-5946. PubMed id: 17004709 DOI: 10.1021/jm060429m
Date:
28-Nov-05     Release date:   06-Dec-05    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
Q57VC7  (Q57VC7_TRYB2) -  Putative uncharacterized protein
Seq:
Struc:
153 a.a.
158 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 3 residue positions (black crosses)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     deoxyribonucleoside monophosphate catabolic process   1 term 
  Biochemical function     nucleoside deoxyribosyltransferase activity     2 terms  

 

 
DOI no: 10.1021/jm060429m J Med Chem 49:5939-5946 (2006)
PubMed id: 17004709  
 
 
Using fragment cocktail crystallography to assist inhibitor design of Trypanosoma brucei nucleoside 2-deoxyribosyltransferase.
J.Bosch, M.A.Robien, C.Mehlin, E.Boni, A.Riechers, F.S.Buckner, W.C.Van Voorhis, P.J.Myler, E.A.Worthey, G.DeTitta, J.R.Luft, A.Lauricella, S.Gulde, L.A.Anderson, O.Kalyuzhniy, H.M.Neely, J.Ross, T.N.Earnest, M.Soltis, L.Schoenfeld, F.Zucker, E.A.Merritt, E.Fan, C.L.Verlinde, W.G.Hol.
 
  ABSTRACT  
 
The 1.8 A resolution de novo structure of nucleoside 2-deoxyribosyltransferase (EC 2.4.2.6) from Trypanosoma brucei (TbNDRT) has been determined by SADa phasing in an unliganded state and several ligand-bound states. This enzyme is important in the salvage pathway of nucleoside recycling. To identify novel lead compounds, we exploited "fragment cocktail soaks". Out of 304 compounds tried in 31 cocktails, four compounds could be identified crystallographically in the active site. In addition, we demonstrated that very short soaks of approximately 10 s are sufficient even for rather hydrophobic ligands to bind in the active site groove, which is promising for the application of similar soaking experiments to less robust crystals of other proteins.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
20471246 C.W.Murray, and T.L.Blundell (2010).
Structural biology in fragment-based drug design.
  Curr Opin Struct Biol, 20, 497-507.  
20048065 J.Fernández-Lucas, C.Acebal, J.V.Sinisterra, M.Arroyo, and I.de la Mata (2010).
Lactobacillus reuteri 2'-deoxyribosyltransferase, a novel biocatalyst for tailoring of nucleosides.
  Appl Environ Microbiol, 76, 1462-1470.  
22184476 J.R.Luft, N.M.Furlani, R.E.Nemoyer, E.J.Penna, J.R.Wolfley, M.E.Snell, S.A.Potter, and E.H.Snell (2010).
Crystal cookery - using high-throughput technologies and the grocery store as a teaching tool.
  J Appl Crystallogr, 43, 1189-1207.  
20642456 N.Drinkwater, H.Vu, K.M.Lovell, K.R.Criscione, B.M.Collins, T.E.Prisinzano, S.A.Poulsen, M.J.McLeish, G.L.Grunewald, and J.L.Martin (2010).
Fragment-based screening by X-ray crystallography, MS and isothermal titration calorimetry to identify PNMT (phenylethanolamine N-methyltransferase) inhibitors.
  Biochem J, 431, 51-61.
PDB codes: 3kpj 3kpu 3kpv 3kpw 3kpy 3kqm 3kqo 3kqp 3kqq 3kqs 3kqt 3kqv 3kqw 3kqy 3kr0 3kr1 3kr2
19929835 C.L.Verlinde, E.Fan, S.Shibata, Z.Zhang, Z.Sun, W.Deng, J.Ross, J.Kim, L.Xiao, T.L.Arakaki, J.Bosch, J.M.Caruthers, E.T.Larson, I.Letrong, A.Napuli, A.Kelly, N.Mueller, F.Zucker, W.C.Van Voorhis, E.A.Merritt, and W.G.Hol (2009).
Fragment-based cocktail crystallography by the medical structural genomics of pathogenic protozoa consortium.
  Curr Top Med Chem, 9, 1678-1687.  
19618939 D.R.Davies, B.Mamat, O.T.Magnusson, J.Christensen, M.H.Haraldsson, R.Mishra, B.Pease, E.Hansen, J.Singh, D.Zembower, H.Kim, A.S.Kiselyov, A.B.Burgin, M.E.Gurney, and L.J.Stewart (2009).
Discovery of leukotriene A4 hydrolase inhibitors using metabolomics biased fragment crystallography.
  J Med Chem, 52, 4694-4715.
PDB codes: 3fts 3ftu 3ftv 3ftw 3ftx 3fty 3fu0 3fu3 3fu5 3fu6 3fud 3fue 3fuf 3fuh 3fui 3fuj 3fuk 3fum 3fun
19855826 W.C.Van Voorhis, W.G.Hol, P.J.Myler, and L.J.Stewart (2009).
The role of medical structural genomics in discovering new drugs for infectious diseases.
  PLoS Comput Biol, 5, e1000530.
PDB codes: 3eiy 3ej0
18676450 J.D.Bauman, K.Das, W.C.Ho, M.Baweja, D.M.Himmel, A.D.Clark, D.A.Oren, P.L.Boyer, S.H.Hughes, A.J.Shatkin, and E.Arnold (2008).
Crystal engineering of HIV-1 reverse transcriptase for structure-based drug design.
  Nucleic Acids Res, 36, 5083-5092.
PDB code: 3dlk
18282486 J.Weigelt, L.D.McBroom-Cerajewski, M.Schapira, Y.Zhao, C.H.Arrowsmith, and C.H.Arrowmsmith (2008).
Structural genomics and drug discovery: all in the family.
  Curr Opin Chem Biol, 12, 32-39.  
18250627 K.U.Wendt, M.S.Weiss, P.Cramer, and D.W.Heinz (2008).
Structures and diseases.
  Nat Struct Mol Biol, 15, 117-120.  
18487606 P.A.Kaminski, P.Dacher, L.Dugué, and S.Pochet (2008).
In vivo reshaping the catalytic site of nucleoside 2'-deoxyribosyltransferase for dideoxy- and didehydronucleosides via a single amino acid substitution.
  J Biol Chem, 283, 20053-20059.  
17851109 H.Jhoti, A.Cleasby, M.Verdonk, and G.Williams (2007).
Fragment-based screening using X-ray crystallography and NMR spectroscopy.
  Curr Opin Chem Biol, 11, 485-493.  
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.