PDBsum entry 1azg

Complex (phosphotransferase/peptide)

PDB id: 1azg

Contents

Protein chains

14 a.a. *

58 a.a. *

* Residue conservation analysis

References listed in PDB file

Key reference

Title

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.

Authors

D.A.Renzoni, D.J.Pugh, G.Siligardi, P.Das, C.J.Morton, C.Rossi, M.D.Waterfield, I.D.Campbell, J.E.Ladbury.

Ref.

Biochemistry, 1996, 35, 15646-15653. [DOI no: 10.1021/bi9620969]

PubMed id

8961927

Abstract

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.

Secondary reference #1

Title

Solution structure and peptide binding of the sh3 domain from human fyn.

Authors

C.J.Morton, D.J.Pugh, E.L.Brown, J.D.Kahmann, D.A.Renzoni, I.D.Campbell.

Ref.

Structure, 1996, 4, 705-714. [DOI no: 10.1016/S0969-2126(96)00076-7]

PubMed id

8805554

Figure 3.
Figure 3. Diagrammatic representation of the Fyn SH3 structure, showing the position of the two β sheets and the single turn of 3[10] helix. Strands are coloured green in β sheet I and yellow in β sheet II, with the 3[10] helix coloured blue. The N and C termini are indicated. This figure was prepared with the programs MOLSCRIPT [45] and Raster3D [46 and 47]. Figure 3. Diagrammatic representation of the Fyn SH3 structure, showing the position of the two β sheets and the single turn of 3[10] helix. Strands are coloured green in β sheet I and yellow in β sheet II, with the 3[10] helix coloured blue. The N and C termini are indicated. This figure was prepared with the programs MOLSCRIPT [[3]45] and Raster3D [[4]46 and [5]47].

Figure 4.
Figure 4. The structure of the Fyn SH3–peptide 2 complex. The protein is shown as a backbone worm, with residues displaying NOE crosspeaks with the peptide shown as sticks. These are Tyr91 (red), Tyr137 (cyan), Asn136 (yellow) and Trp119 (green). The peptide is displayed as a ball and stick structure, coloured by atom type, with the N terminus on the right of the picture. Figure 4. The structure of the Fyn SH3–peptide 2 complex. The protein is shown as a backbone worm, with residues displaying NOE crosspeaks with the peptide shown as sticks. These are Tyr91 (red), Tyr137 (cyan), Asn136 (yellow) and Trp119 (green). The peptide is displayed as a ball and stick structure, coloured by atom type, with the N terminus on the right of the picture.

The above figures are reproduced from the cited reference with permission from Cell Press