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PDBsum entry 1nlo

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protein Protein-protein interface(s) links
Complex (transferase/peptide) PDB id
1nlo
Jmol
Contents
Protein chains
56 a.a. *
11 a.a. *
* Residue conservation analysis
PDB id:
1nlo
Name: Complex (transferase/peptide)
Title: Structure of signal transduction protein, nmr, minimized average structure
Structure: C-src. Chain: c. Fragment: sh3 domain. Engineered: yes. Nl1 (mn7-mn2-mn1-plpplp). Chain: n. Engineered: yes. Other_details: ligand nl1 contains non-peptide elements
Source: Gallus gallus. Chicken. Organism_taxid: 9031. Gene: chicken. Expressed in: gst-fusion.
NMR struc: 1 models
Authors: S.Feng,T.M.Kapoor,F.Shirai,A.P.Combs,S.L.Schreiber
Key ref: S.Feng et al. (1996). Molecular basis for the binding of SH3 ligands with non-peptide elements identified by combinatorial synthesis. Chem Biol, 3, 661-670. PubMed id: 8807900
Date:
04-Aug-96     Release date:   27-Jan-97    
PROCHECK
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 Headers
 References

Protein chain
Pfam   ArchSchema ?
P00523  (SRC_CHICK) -  Proto-oncogene tyrosine-protein kinase Src
Seq:
Struc:
 
Seq:
Struc:
533 a.a.
56 a.a.
Protein chain
No UniProt id for this chain
Struc: 10 a.a.
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: Chain C: E.C.2.7.10.2  - Non-specific protein-tyrosine kinase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate
ATP
+ [protein]-L-tyrosine
= ADP
+ [protein]-L-tyrosine phosphate
Molecule diagrams generated from .mol files obtained from the KEGG ftp site

 

 
    reference    
 
 
Chem Biol 3:661-670 (1996)
PubMed id: 8807900  
 
 
Molecular basis for the binding of SH3 ligands with non-peptide elements identified by combinatorial synthesis.
S.Feng, T.M.Kapoor, F.Shirai, A.P.Combs, S.L.Schreiber.
 
  ABSTRACT  
 
BACKGROUND: Protein-structure-based combinatorial chemistry has recently been used to discover several ligands containing non-peptide binding elements to the Src SH3 domain. The encoded library used has the form Cap-M1-M2-M3-PLPPLP, in which the Cap and Mi's are composed of a diverse set of organic monomers. The PLPPLP portion provided a structural bias directing the non-peptide fragment Cap-M1-M2-M3 to the SH3 specificity pocket. Fifteen ligands were selected from > 1.1 million distinct compounds. The structural basis for selection was unknown. RESULTS: The solution structures of the Src SH3 domain complexed with two ligands containing non-peptide elements selected from the library were determined by multidimensional NMR spectroscopy. The non-peptide moieties of the ligands interact with the specificity pocket of Src SH3 domain differently from peptides complexed with SH3 domains. Structural information about the ligands was used to design various homologs, whose affinities for the SH3 domain were measured. The results provide a structural basis for understanding the selection of a few optimal ligands from a large library. CONCLUSIONS: The cycle of protein-structure-based combinatorial chemistry followed by structure determination of the few highest affinity ligands provides a powerful new tool for the field of molecular recognition.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
20024074 S.Hoffmann, S.A.Funke, K.Wiesehan, S.Moedder, J.M.Glück, S.Feuerstein, M.Gerdts, J.Mötter, and D.Willbold (2010).
Competitively selected protein ligands pay their increase in specificity by a decrease in affinity.
  Mol Biosyst, 6, 116-123.  
20221255 S.R.McGuffee, and A.H.Elcock (2010).
Diffusion, crowding & protein stability in a dynamic molecular model of the bacterial cytoplasm.
  PLoS Comput Biol, 6, e1000694.  
16407060 F.Ding, K.C.Prutzman, S.L.Campbell, and N.V.Dokholyan (2006).
Topological determinants of protein domain swapping.
  Structure, 14, 5.  
16839198 F.Ding, and N.V.Dokholyan (2006).
Emergence of protein fold families through rational design.
  PLoS Comput Biol, 2, e85.  
15880548 L.J.Ball, R.Kühne, J.Schneider-Mergener, and H.Oschkinat (2005).
Recognition of Proline-Rich Motifs by Protein-Protein-Interaction Domains.
  Angew Chem Int Ed Engl, 44, 2852-2869.  
15377393 W.Cai, J.Pei, and N.V.Grishin (2004).
Reconstruction of ancestral protein sequences and its applications.
  BMC Evol Biol, 4, 33.  
12833568 F.Santamaria, Z.Wu, C.Boulègue, G.Pál, and W.Lu (2003).
Reexamination of the recognition preference of the specificity pocket of the Abl SH3 domain.
  J Mol Recognit, 16, 131-138.  
11682324 M.Vidal, V.Gigoux, and C.Garbay (2001).
SH2 and SH3 domains as targets for anti-proliferative agents.
  Crit Rev Oncol Hematol, 40, 175-186.  
10467125 B.Aghazadeh, and M.K.Rosen (1999).
Ligand recognition by SH3 and WW domains: the role of N-alkylation in PPII helices.
  Chem Biol, 6, R241-R246.  
  10233922 J.C.Albrecht, U.Friedrich, C.Kardinal, J.Koehn, B.Fleckenstein, S.M.Feller, and B.Biesinger (1999).
Herpesvirus ateles gene product Tio interacts with nonreceptor protein tyrosine kinases.
  J Virol, 73, 4631-4639.  
9566119 D.C.Dalgarno, M.C.Botfield, and R.J.Rickles (1997).
SH3 domains and drug design: ligands, structure, and biological function.
  Biopolymers, 43, 383-400.  
9408950 H.V.Patel, S.R.Tzeng, C.Y.Liao, S.H.Chen, and J.W.Cheng (1997).
SH3 domain of Bruton's tyrosine kinase can bind to proline-rich peptides of TH domain of the kinase and p120cbl.
  Proteins, 29, 545-552.  
9425659 R.E.Hubbard (1997).
Can drugs be designed?
  Curr Opin Biotechnol, 8, 696-700.  
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.