PDBsum entry 1a0n

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protein Protein-protein interface(s) links
Complex (phosphotransferase/peptide) PDB id
Protein chains
14 a.a.
58 a.a. *
* Residue conservation analysis
PDB id:
Name: Complex (phosphotransferase/peptide)
Title: Nmr study of the sh3 domain from fyn proto-oncogene tyrosine kinase complexed with the synthetic peptide p2l corresponding to residues 91-104 of the p85 subunit of pi3- kinase, family of 25 structures
Structure: Pro-pro-arg-pro-leu-pro-val-ala-pro-gly-ser-ser- lys-thr. Chain: a. Fragment: p85 subunit of pi3-kinase, residues 91 - 104. Synonym: p2l. Engineered: yes. Fyn. Chain: b. Fragment: sh3 domain, residues 82 - 148.
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 469008.
NMR struc: 25 models
Authors: D.A.Renzoni,D.J.R.Pugh,G.Siligardi,P.Das,C.J.Morton,C.Rossi, M.D.Waterfield,I.D.Campbell,J.E.Ladbury
Key ref:
D.A.Renzoni et al. (1996). Structural and thermodynamic characterization of the interaction of the SH3 domain from Fyn with the proline-rich binding site on the p85 subunit of PI3-kinase. Biochemistry, 35, 15646-15653. PubMed id: 8961927 DOI: 10.1021/bi9620969
05-Dec-97     Release date:   25-Feb-98    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P27986  (P85A_HUMAN) -  Phosphatidylinositol 3-kinase regulatory subunit alpha
724 a.a.
14 a.a.
Protein chain
Pfam   ArchSchema ?
P06241  (FYN_HUMAN) -  Tyrosine-protein kinase Fyn
537 a.a.
58 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

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


DOI no: 10.1021/bi9620969 Biochemistry 35:15646-15653 (1996)
PubMed id: 8961927  
Structural and thermodynamic characterization of the interaction of the SH3 domain from Fyn with the proline-rich binding site on the p85 subunit of PI3-kinase.
D.A.Renzoni, D.J.Pugh, G.Siligardi, P.Das, C.J.Morton, C.Rossi, M.D.Waterfield, I.D.Campbell, J.E.Ladbury.
The interaction of the Fyn SH3 domain with the p85 subunit of PI3-kinase is investigated using structural detail and thermodynamic data. The solution structure complex of the SH3 domain with a proline-rich peptide mimic of the binding site on the p85 subunit is described. This indicates that the peptide binds as a poly(L-proline) type II helix. Circular dichroism spectroscopic studies reveal that in the unbound state the peptide exhibits no structure. Thermodynamic data for the binding of this peptide to the SH3 domain suggest that the weak binding (approximately 31 microM) of this interaction is, in part, due to the entropically unfavorable effect of helix formation (delta S0 = -78 J.mol-1.K-1). Binding of the SH3 domain to the intact p85 subunit (minus its own SH3 domain) is tighter, and the entropic and enthalpic contributions are very different from those given by the peptide interaction (delta S0 = +252 J.mol-1.K-1; delta H0 = +44 kJ.mol-1). From these dramatically different thermodynamic measurements we are able to conclude that the interaction of the proline-rich peptide does not effectively mimic the interaction of the intact p85 subunit with the SH3 domain and suggest that other interactions could be important.

Literature references that cite this PDB file's key reference

  PubMed id Reference
19906645 A.Palencia, A.Camara-Artigas, M.T.Pisabarro, J.C.Martinez, and I.Luque (2010).
Role of interfacial water molecules in proline-rich ligand recognition by the Src homology 3 domain of Abl.
  J Biol Chem, 285, 2823-2833.
PDB codes: 3eg0 3eg1 3eg2 3eg3 3egu
19921743 C.Rubini, P.Ruzza, M.R.Spaller, G.Siligardi, R.Hussain, D.G.Udugamasooriya, M.Bellanda, S.Mammi, A.Borgogno, A.Calderan, L.Cesaro, A.M.Brunati, and A.Donella-Deana (2010).
Recognition of lysine-rich peptide ligands by murine cortactin SH3 domain: CD, ITC, and NMR studies.
  Biopolymers, 94, 298-306.  
19323566 C.B.McDonald, K.L.Seldeen, B.J.Deegan, and A.Farooq (2009).
SH3 domains of Grb2 adaptor bind to PXpsiPXR motifs within the Sos1 nucleotide exchange factor in a discriminate manner.
  Biochemistry, 48, 4074-4085.  
19208197 P.L.Elkin, M.S.Tuttle, B.E.Trusko, and S.H.Brown (2009).
BioProspecting: novel marker discovery obtained by mining the bibleome.
  BMC Bioinformatics, 10, S9.  
18467332 C.H.Reynolds, C.J.Garwood, S.Wray, C.Price, S.Kellie, T.Perera, M.Zvelebil, A.Yang, P.W.Sheppard, I.M.Varndell, D.P.Hanger, and B.H.Anderton (2008).
Phosphorylation regulates tau interactions with Src homology 3 domains of phosphatidylinositol 3-kinase, phospholipase Cgamma1, Grb2, and Src family kinases.
  J Biol Chem, 283, 18177-18186.  
18721137 S.A.Solheim, E.Petsalaki, A.J.Stokka, R.B.Russell, K.Taskén, and T.Berge (2008).
Interactions between the Fyn SH3-domain and adaptor protein Cbp/PAG derived ligands, effects on kinase activity and affinity.
  FEBS J, 275, 4863-4874.  
17407569 S.Casares, E.Ab, H.Eshuis, O.Lopez-Mayorga, N.A.van Nuland, and F.Conejero-Lara (2007).
The high-resolution NMR structure of the R21A Spc-SH3:P41 complex: understanding the determinants of binding affinity by comparison with Abl-SH3.
  BMC Struct Biol, 7, 22.
PDB codes: 2jm8 2jm9 2jma
17330285 S.Casares, O.López-Mayorga, M.C.Vega, A.Cámara-Artigas, and F.Conejero-Lara (2007).
Cooperative propagation of local stability changes from low-stability and high-stability regions in a SH3 domain.
  Proteins, 67, 531-547.
PDB codes: 2cdt 2f2v 2f2w 2f2x
16506148 P.Ruzza, G.Siligardi, A.Donella-Deana, A.Calderan, R.Hussain, C.Rubini, L.Cesaro, A.Osler, A.Guiotto, L.A.Pinna, and G.Borin (2006).
4-Fluoroproline derivative peptides: effect on PPII conformation and SH3 affinity.
  J Pept Sci, 12, 462-471.  
16571873 R.X.Song, and R.J.Santen (2006).
Membrane initiated estrogen signaling in breast cancer.
  Biol Reprod, 75, 9.  
15834155 E.Solomaha, F.L.Szeto, M.A.Yousef, and H.C.Palfrey (2005).
Kinetics of Src homology 3 domain association with the proline-rich domain of dynamins: specificity, occlusion, and the effects of phosphorylation.
  J Biol Chem, 280, 23147-23156.  
16257377 G.A.Holdgate, and W.H.Ward (2005).
Measurements of binding thermodynamics in drug discovery.
  Drug Discov Today, 10, 1543-1550.  
16126407 R.X.Song, Z.Zhang, and R.J.Santen (2005).
Estrogen rapid action via protein complex formation involving ERalpha and Src.
  Trends Endocrinol Metab, 16, 347-353.  
15459337 J.A.Knappenberger, C.M.Kraemer-Pecore, and J.T.Lecomte (2004).
Insertion of the cytochrome b5 heme-binding loop into an SH3 domain. Effects on structure and stability, and clues about the cytochrome's architecture.
  Protein Sci, 13, 2899-2908.  
15489226 M.Katragadda, D.Morikis, and J.D.Lambris (2004).
Thermodynamic studies on the interaction of the third complement component and its inhibitor, compstatin.
  J Biol Chem, 279, 54987-54995.  
15007077 T.Hori, T.Yokomizo, H.Ago, M.Sugahara, G.Ueno, M.Yamamoto, T.Kumasaka, T.Shimizu, and M.Miyano (2004).
Structural basis of leukotriene B4 12-hydroxydehydrogenase/15-Oxo-prostaglandin 13-reductase catalytic mechanism and a possible Src homology 3 domain binding loop.
  J Biol Chem, 279, 22615-22623.
PDB codes: 1v3t 1v3u 1v3v
12717021 J.C.Ferreon, and V.J.Hilser (2003).
Ligand-induced changes in dynamics in the RT loop of the C-terminal SH3 domain of Sem-5 indicate cooperative conformational coupling.
  Protein Sci, 12, 982-996.  
12874286 K.Kowanetz, I.Szymkiewicz, K.Haglund, M.Kowanetz, K.Husnjak, J.D.Taylor, P.Soubeyran, U.Engstrom, J.E.Ladbury, and I.Dikic (2003).
Identification of a novel proline-arginine motif involved in CIN85-dependent clustering of Cbl and down-regulation of epidermal growth factor receptors.
  J Biol Chem, 278, 39735-39746.  
12395395 B.Bochicchio, and A.M.Tamburro (2002).
Polyproline II structure in proteins: identification by chiroptical spectroscopies, stability, and functions.
  Chirality, 14, 782-792.  
11916974 G.Siligardi, B.Panaretou, P.Meyer, S.Singh, D.N.Woolfson, P.W.Piper, L.H.Pearl, and C.Prodromou (2002).
Regulation of Hsp90 ATPase activity by the co-chaperone Cdc37p/p50cdc37.
  J Biol Chem, 277, 20151-20159.  
11750878 J.M.Ellery, and P.J.Nicholls (2002).
Alternate signalling pathways from the interleukin-2 receptor.
  Cytokine Growth Factor Rev, 13, 27-40.  
11955060 K.Schweimer, S.Hoffmann, F.Bauer, U.Friedrich, C.Kardinal, S.M.Feller, B.Biesinger, and H.Sticht (2002).
Structural investigation of the binding of a herpesviral protein to the SH3 domain of tyrosine kinase Lck.
  Biochemistry, 41, 5120-5130.
PDB codes: 1h92 1wa7
11141062 N.Okishio, T.Tanaka, R.Fukuda, and M.Nagai (2001).
Role of the conserved acidic residue Asp21 in the structure of phosphatidylinositol 3-kinase Src homology 3 domain: circular dichroism and nuclear magnetic resonance studies.
  Biochemistry, 40, 119-129.  
10869177 J.A.Bousquet, C.Garbay, B.P.Roques, and Y.Mély (2000).
Circular dichroic investigation of the native and non-native conformational states of the growth factor receptor-binding protein 2 N-terminal src homology domain 3: effect of binding to a proline-rich peptide from guanine nucleotide exchange factor.
  Biochemistry, 39, 7722-7735.  
10662684 J.E.Ladbury, and S.Arold (2000).
Searching for specificity in SH domains.
  Chem Biol, 7, R3-R8.  
10383400 D.Ron, E.W.Napolitano, A.Voronova, N.J.Vasquez, D.N.Roberts, B.L.Calio, R.H.Caothien, S.M.Pettiford, S.Wellik, J.B.Mandac, and L.M.Kauvar (1999).
Direct interaction in T-cells between thetaPKC and the tyrosine kinase p59fyn.
  J Biol Chem, 274, 19003-19010.  
9485402 K.W.Plaxco, J.I.Guijarro, C.J.Morton, M.Pitkeathly, I.D.Campbell, and C.M.Dobson (1998).
The folding kinetics and thermodynamics of the Fyn-SH3 domain.
  Biochemistry, 37, 2529-2537.  
9478994 M.Vidal, J.L.Montiel, D.Cussac, F.Cornille, M.Duchesne, F.Parker, B.Tocqué, B.P.Roques, and C.Garbay (1998).
Differential interactions of the growth factor receptor-bound protein 2 N-SH3 domain with son of sevenless and dynamin. Potential role in the Ras-dependent signaling pathway.
  J Biol Chem, 273, 5343-5348.  
9778343 S.Arold, R.O'Brien, P.Franken, M.P.Strub, F.Hoh, C.Dumas, and J.E.Ladbury (1998).
RT loop flexibility enhances the specificity of Src family SH3 domains for HIV-1 Nef.
  Biochemistry, 37, 14683-14691.
PDB code: 1bu1
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.  
9351809 S.Arold, P.Franken, M.P.Strub, F.Hoh, S.Benichou, R.Benarous, and C.Dumas (1997).
The crystal structure of HIV-1 Nef protein bound to the Fyn kinase SH3 domain suggests a role for this complex in altered T cell receptor signaling.
  Structure, 5, 1361-1372.
PDB codes: 1avv 1avz
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.