1AP7

P19-INK4D FROM MOUSE, NMR, 20 STRUCTURES

Summary for 1AP7

• Entry DOI: 10.2210/pdb1ap7/pdb
• Descriptor: P19-INK4D (1 entity in total)
• Functional Keywords: cell cycle inhibitor, cyclin dependent kinase inhibitor, ink, cdki, ankyrin repeat
• Biological source: Mus musculus (house mouse)
• Total number of polymer chains: 1
• Total formula weight: 17976.51

Authors

Archer, S.J.,Luh, F.Y.,Domaille, P.J.,Smith, B.O.,Laue, E.D. (deposition date: 1997-07-25, release date: 1998-09-16, Last modification date: 2024-05-22)

Primary citation

Luh, F.Y.,Archer, S.J.,Domaille, P.J.,Smith, B.O.,Owen, D.,Brotherton, D.H.,Raine, A.R.,Xu, X.,Brizuela, L.,Brenner, S.L.,Laue, E.D.
Structure of the cyclin-dependent kinase inhibitor p19Ink4d.
Nature, 389:999-1003, 1997

PubMed Abstract: In cancer, the biochemical pathways that are dominated by the two tumour-suppressor proteins, p53 and Rb, are the most frequently disrupted. Cyclin D-dependent kinases phosphorylate Rb to control its activity and they are, in turn, specifically inhibited by the Ink4 family of cyclin-dependent kinase inhibitors (CDKIs) which cause arrest at the G1 phase of the cell cycle. Mutations in Rb, cyclin D1, its catalytic subunit Cdk4, and the CDKI p16Ink4a, which alter the protein or its level of expression, are all strongly implicated in cancer. This suggests that the Rb 'pathway' is of particular importance. Here we report the structure of the p19Ink4d protein, determined by NMR spectroscopy. The structure indicates that most mutations to the p16Ink4a gene, which result in loss of function, are due to incorrectly folded and/or insoluble proteins. We propose a model for the interaction of Ink4 proteins with D-type cyclin-Cdk4/6 complexes that might provide a basis for the design of therapeutics against cancer. The sequences of the Ink4 family of CDKIs are highly conserved

PubMed: 9353127
DOI: 10.1038/40202

Experimental method

SOLUTION NMR