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1ap7
From Proteopedia
| 1ap7, 20 NMR models () | |||||||||
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| Resources: | FirstGlance, OCA, RCSB, PDBsum | ||||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||||
P19-INK4D FROM MOUSE, NMR, 20 STRUCTURES
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
Structure of the cyclin-dependent kinase inhibitor p19Ink4d., Luh FY, Archer SJ, Domaille PJ, Smith BO, Owen D, Brotherton DH, Raine AR, Xu X, Brizuela L, Brenner SL, Laue ED, Nature. 1997 Oct 30;389(6654):999-1003. PMID:9353127
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
About this Structure
1ap7 is a 1 chain structure with sequence from Mus musculus. Full experimental information is available from OCA.
Reference
- Luh FY, Archer SJ, Domaille PJ, Smith BO, Owen D, Brotherton DH, Raine AR, Xu X, Brizuela L, Brenner SL, Laue ED. Structure of the cyclin-dependent kinase inhibitor p19Ink4d. Nature. 1997 Oct 30;389(6654):999-1003. PMID:9353127 doi:10.1038/40202
