1okv
From Proteopedia
(New page: 200px<br /> <applet load="1okv" size="450" color="white" frame="true" align="right" spinBox="true" caption="1okv, resolution 2.40Å" /> '''CYCLIN A BINDING GR...) |
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| - | [[Image:1okv.gif|left|200px]]<br /> | + | [[Image:1okv.gif|left|200px]]<br /><applet load="1okv" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1okv" size=" | + | |
caption="1okv, resolution 2.40Å" /> | caption="1okv, resolution 2.40Å" /> | ||
'''CYCLIN A BINDING GROOVE INHIBITOR H-ARG-ARG-LEU-ILE-PHE-NH2'''<br /> | '''CYCLIN A BINDING GROOVE INHIBITOR H-ARG-ARG-LEU-ILE-PHE-NH2'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Inhibition of CDK2/CA (cyclin-dependent kinase 2/cyclin A complex) | + | 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. |
==About this Structure== | ==About this Structure== | ||
| - | 1OKV is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with NH2 as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] Full crystallographic information is available from [http:// | + | 1OKV is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=NH2:'>NH2</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1OKV OCA]. |
==Reference== | ==Reference== | ||
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[[Category: peptidomimetics]] | [[Category: peptidomimetics]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:18:51 2008'' |
Revision as of 12:18, 21 February 2008
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CYCLIN A BINDING GROOVE INHIBITOR H-ARG-ARG-LEU-ILE-PHE-NH2
Overview
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.
About this Structure
1OKV is a Protein complex structure of sequences from Homo sapiens with as ligand. Active as Non-specific serine/threonine protein kinase, with EC number 2.7.11.1 Full crystallographic information is available from OCA.
Reference
Insights into cyclin groove recognition: complex crystal structures and inhibitor design through ligand exchange., Kontopidis G, Andrews MJ, McInnes C, Cowan A, Powers H, Innes L, Plater A, Griffiths G, Paterson D, Zheleva DI, Lane DP, Green S, Walkinshaw MD, Fischer PM, Structure. 2003 Dec;11(12):1537-46. PMID:14656438
Page seeded by OCA on Thu Feb 21 14:18:51 2008
Categories: Homo sapiens | Non-specific serine/threonine protein kinase | Protein complex | Andrews, M. | Cowan, A. | Fischer, P. | Green, S. | Griffiths, G. | Innes, L. | Kontopidis, G. | Lane, D. | Mcinnes, C. | Paterson, D. | Plater, A. | Powers, H. | Walkinshaw, M. | Zheleva, D. | NH2 | Cell cycle | Cyclin a | Drug design | Inhibitor | Kinase | Ligand exchange | Peptidomimetics
