1OL2

Cyclin A binding groove inhibitor H-Arg-Arg-Leu-Asn-(p-F-Phe)-NH2

Summary for 1OL2

• Entry DOI: 10.2210/pdb1ol2/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 1H06 1H07 1H08 1H0U 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 1OKU 1OKV 1OKW 1OL1 1P2A 1P5E 1PKD 1QMZ
• Descriptor: CELL DIVISION PROTEIN KINASE 2, CYCLIN A2, ARG-ARG-LEU-ASN-PFF-NH2, ... (4 entities in total)
• Functional Keywords: cell cycle, transferase-transferase inhibitor complex, cyclin a, ligand exchange, peptidomimetics, kinase, transferase/transferase inhibitor
• Biological source: HOMO SAPIENS (HUMAN); More
• Cellular location: Cytoplasm, cytoskeleton, microtubule organizing center, centrosome: P24941; Nucleus : P20248
• Total number of polymer chains: 6
• Total formula weight: 129133.67

Authors

Kontopidis, G.,Andrews, M.,McInnes, C.,Cowan, A.,Powers, H.,Innes, L.,Plater, A.,Griffiths, G.,Paterson, D.,Zheleva, D.,Lane, D.,Green, S.,Walkinshaw, M.,Fischer, P. (deposition date: 2003-08-05, release date: 2003-12-11, Last modification date: 2023-12-13)

Primary citation

Kontopidis, G.,Andrews, M.,Mcinnes, C.,Cowan, A.,Powers, H.,Innes, L.,Plater, A.,Griffiths, G.,Paterson, D.,Zheleva, D.,Lane, D.,Green, S.,Walkinshaw, M.,Fischer, P.
Insights Into Cyclin Groove Recognition. Complex Crystal Structures and Inhibitor Design Through Ligand Exchange
Structure, 11:1537-, 2003

PubMed Abstract: Inhibition of CDK2/CA (cyclin-dependent kinase 2/cyclin A complex) activity through blocking of the substrate recognition site in the cyclin A subunit has been demonstrated to be an effective method for inducing apoptosis in tumor cells. We have used the cyclin binding motif (CBM) present in the tumor suppressor proteins p21(WAF1) and p27(KIP1) as a template to optimize the minimal sequence necessary for CDK2/CA inhibition. A series of peptides were prepared, containing nonnatural amino acids, which possess nano- to micromolar CDK2-inhibitory activity. Here we present X-ray structures of the protein complex CDK2/CA, together with the cyclin groove-bound peptides H-Ala-Ala-Abu-Arg-Ser-Leu-Ile-(p-F-Phe)-NH(2) (peptide 1), H-Arg-Arg-Leu-Ile-Phe-NH(2) (peptide 2), Ac-Arg-Arg-Leu-Asn-(m-Cl-Phe)-NH(2) (peptide 3), H-Arg-Arg-Leu-Asn-(p-F-Phe)-NH(2) (peptide 4), and H-Cit-Cit-Leu-Ile-(p-F-Phe)-NH(2) (peptide 5). Some of the peptide complexes presented here were obtained through the novel technique of ligand exchange within protein crystals. This method may find general application for obtaining complex structures of proteins with surface-bound ligands.

PubMed: 14656438
DOI: 10.1016/J.STR.2003.11.006

Experimental method

X-RAY DIFFRACTION (2.6 Å)