PDBsum entry 2a5e

Anti-oncogene

PDB id: 2a5e

Contents

Protein chain

156 a.a.

References listed in PDB file

Key reference

Title

Tumor suppressor p16ink4a: determination of solution structure and analyses of its interaction with cyclin-Dependent kinase 4.

Authors

I.J.Byeon, J.Li, K.Ericson, T.L.Selby, A.Tevelev, H.J.Kim, P.O'Maille, M.D.Tsai.

Ref.

Mol Cell, 1998, 1, 421-431. [DOI no: 10.1016/S1097-2765(00)80042-8]

PubMed id

9660926

Abstract

The solution structure of the tumor suppressor p16INK4A has been determined by NMR, and important recognition regions of both cdk4 and p16INK4A have been identified. The tertiary structure of p16INK4A contains four helix-turn-helix motifs linked by three loops. Twelve tumorigenic mutants of p16INK4A have been constructed and analyzed for their structure and activity, and new mutants have been designed rationally. A fragment of 58 residues at the N terminus of cdk4 important for p16INK4A binding has been identified. The importance of this region was further verified by mutational analysis of cdk4. These results and docking experiments have been used to assess possible modes of binding between p16INK4A and cdk4.

Figure 4.
Figure 4. Assay of p16 ActivityGels of in vitro phosphorylation of pRb by cdk4 in the presence of increasing concentrations of wild-type p16 (A) and D84H (B). Lanes 1 and 2 are negative controls.

Figure 7.
Figure 7. Working Model for the C5–p16 ComplexThe model is depicted such that the ionic interactions between specific charged residues are visible. Side chains of Arg-24 and Glu-7 of C5 (blue ribbon) are shown in ball-and-stick mode. The p16 residue facing C5/Arg-24 is Glu-69, and that facing C5/Glu-7 is Arg-47. C5/Lys-22 could interact with p16/Asp-74. The p16 structure shown is 140° rotated from that in Figure 3B.

The above figures are reprinted by permission from Cell Press: Mol Cell (1998, 1, 421-431) copyright 1998.