2CJM

Mechanism of CDK inhibition by active site phosphorylation: CDK2 Y15p T160p in complex with cyclin A structure

Summary for 2CJM

• Entry DOI: 10.2210/pdb2cjm/pdb
• Related: 1AQ1 1B38 1B39 1BUH 1CKP 1DI8 1DM2 1E1V 1E1X 1E9H 1F5Q 1FIN 1FQ1 1FVT 1FVV 1G5S 1GIH 1GII 1GIJ 1GY3 1GZ8 1H00 1H01 1H07 1H08 1H0V 1H0W 1H1P 1H1Q 1H1R 1H1S 1H24 1H25 1H26 1H27 1H28 1HCK 1HCL 1JST 1JSU 1JSV 1JVP 1KE5 1KE6 1KE7 1KE8 1KE9 1OGU 1OI9 1OIQ 1OIR 1OIT 1OIU 1OIY 1OKV 1OKW 1OL1 1OL2 1P2A 1P5E 1PF8 1PKD 1PW2 1PXI 1PXJ 1PXK 1PXL 1PXM 1PXN 1PXO 1PXP 1PYE 1QMZ 1R78 1URC 1URW 1V1K 1VYW 1VYZ 1W0X 1W8C 1W98 1WCC 1Y8Y 1Y91 1YKR 2A0C 2B52 2B53 2B54 2B55 2BHE 2BHH 2BKZ 2BPM 2BTR 2BTS 2C4G 2C5N 2C5O 2C5P 2C5T 2C5V 2C5X 2C5Y 2C68 2C69 2C6I 2C6K 2C6L 2C6M 2C6O 2C6T 2CCH 2CCI 2EXM
• Descriptor: CELL DIVISION PROTEIN KINASE 2, CYCLIN A2, ADENOSINE-5'-TRIPHOSPHATE, ... (5 entities in total)
• Functional Keywords: phosphorylation, nucleotide-binding, mitosis, cell cycle, regulation, serine/threonine-protein kinase, atp-binding, transferase, cell division, cyclin-dependent kinase, complex (transferase-cell division)
• Biological source: HOMO SAPIENS (HUMAN); More
• Cellular location: Cytoplasm, cytoskeleton, microtubule organizing center, centrosome: P24941; Nucleus : P20248
• Total number of polymer chains: 4
• Total formula weight: 128560.16

Authors

Welburn, J.P.I.,Tucker, J.,Johnson, T.,Lindert, L.,Morgan, M.,Willis, A.,Noble, M.E.M.,Endicott, J.A. (deposition date: 2006-04-05, release date: 2006-04-24, Last modification date: 2024-10-23)

Primary citation

Welburn, J.P.I.,Tucker, J.,Johnson, T.,Lindert, L.,Morgan, M.,Willis, A.,Noble, M.E.M.,Endicott, J.A.
How Tyrosine 15 Phosphorylation Inhibits the Activity of Cyclin-Dependent Kinase 2-Cyclin A.
J.Biol.Chem., 282:3173-, 2007

PubMed Abstract: Inhibition of cyclin-dependent kinase 1 (CDK1) activity by Tyr-15 phosphorylation directly regulates entry into mitosis and is an important element in the control of the unperturbed cell cycle. Active site phosphorylation of other members of the CDK family that regulate cell cycle progression instates checkpoints that are fundamental to eukaryotic cell cycle regulation. Kinetic and crystallographic analyses of CDK2-cyclin A complexes reveal that this inhibitory mechanism operates through steric blockade of peptide substrate binding and through the creation of an environment that favors a non-productive conformation of the terminal group of ATP. By contrast, tyrosine phosphorylation of CDK2 alters neither its Km for ATP nor its significant intrinsic ATPase activity. Tyr-15-phosphorylated CDK2 retains trace protein phosphorylation activity that should be considered in quantitative and qualitative cell cycle models.

PubMed: 17095507
DOI: 10.1074/JBC.M609151200

Experimental method

X-RAY DIFFRACTION (2.3 Å)