1pf8
From Proteopedia
(New page: 200px<br /> <applet load="1pf8" size="450" color="white" frame="true" align="right" spinBox="true" caption="1pf8, resolution 2.51Å" /> '''Crystal Structure o...) |
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| - | [[Image:1pf8.gif|left|200px]]<br /> | + | [[Image:1pf8.gif|left|200px]]<br /><applet load="1pf8" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1pf8" size=" | + | |
caption="1pf8, resolution 2.51Å" /> | caption="1pf8, resolution 2.51Å" /> | ||
'''Crystal Structure of Human Cyclin-Dependent Kinase 2 Complexed with a Nucleoside Inhibitor'''<br /> | '''Crystal Structure of Human Cyclin-Dependent Kinase 2 Complexed with a Nucleoside Inhibitor'''<br /> | ||
==Overview== | ==Overview== | ||
| - | SU9516 is a 3-substituted indolinone compound with demonstrated potent and | + | SU9516 is a 3-substituted indolinone compound with demonstrated potent and selective inhibition toward cyclin dependent kinases (cdks). Here, we describe the kinetic characterization of this inhibition with respect to cdk2, 1, and 4, along with the crystal structure in complex with cdk2. The molecule is competitive with respect to ATP for cdk2/cyclin A, with a K(i) value of 0.031 microM. Similarly, SU9516 inhibits cdk2/cyclin E and cdk1/cyclin B1 in an ATP-competitive manner, although at a 2- to 8-fold reduced potency. In contrast, the compound exhibited non-competitive inhibition with respect to ATP toward cdk4/cyclin D1, with a 45-fold reduced potency. The X-ray crystal structure of SU9516 bound to cdk2 revealed interactions between the molecule and Leu83 and Glu81 of the kinase. This study should aid in the development of more potent and selective cdk inhibitors for potential therapeutic agents. |
==About this Structure== | ==About this Structure== | ||
| - | 1PF8 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with SU9 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:// | + | 1PF8 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=SU9:'>SU9</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=1PF8 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Non-specific serine/threonine protein kinase]] | [[Category: Non-specific serine/threonine protein kinase]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Bellamacina, R | + | [[Category: Bellamacina, R C.]] |
| - | [[Category: Boisvert, D | + | [[Category: Boisvert, D C.]] |
[[Category: Huang, P.]] | [[Category: Huang, P.]] | ||
[[Category: Hui, T.]] | [[Category: Hui, T.]] | ||
[[Category: Jancarik, J.]] | [[Category: Jancarik, J.]] | ||
| - | [[Category: Kim, S | + | [[Category: Kim, S H.]] |
| - | [[Category: Moshinsky, D | + | [[Category: Moshinsky, D J.]] |
| - | [[Category: Rice, A | + | [[Category: Rice, A G.]] |
[[Category: SU9]] | [[Category: SU9]] | ||
[[Category: atp-binding]] | [[Category: atp-binding]] | ||
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[[Category: transferase]] | [[Category: transferase]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:28:08 2008'' |
Revision as of 12:28, 21 February 2008
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Crystal Structure of Human Cyclin-Dependent Kinase 2 Complexed with a Nucleoside Inhibitor
Overview
SU9516 is a 3-substituted indolinone compound with demonstrated potent and selective inhibition toward cyclin dependent kinases (cdks). Here, we describe the kinetic characterization of this inhibition with respect to cdk2, 1, and 4, along with the crystal structure in complex with cdk2. The molecule is competitive with respect to ATP for cdk2/cyclin A, with a K(i) value of 0.031 microM. Similarly, SU9516 inhibits cdk2/cyclin E and cdk1/cyclin B1 in an ATP-competitive manner, although at a 2- to 8-fold reduced potency. In contrast, the compound exhibited non-competitive inhibition with respect to ATP toward cdk4/cyclin D1, with a 45-fold reduced potency. The X-ray crystal structure of SU9516 bound to cdk2 revealed interactions between the molecule and Leu83 and Glu81 of the kinase. This study should aid in the development of more potent and selective cdk inhibitors for potential therapeutic agents.
About this Structure
1PF8 is a Single protein structure of sequence 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
SU9516: biochemical analysis of cdk inhibition and crystal structure in complex with cdk2., Moshinsky DJ, Bellamacina CR, Boisvert DC, Huang P, Hui T, Jancarik J, Kim SH, Rice AG, Biochem Biophys Res Commun. 2003 Oct 24;310(3):1026-31. PMID:14550307
Page seeded by OCA on Thu Feb 21 14:28:08 2008
Categories: Homo sapiens | Non-specific serine/threonine protein kinase | Single protein | Bellamacina, R C. | Boisvert, D C. | Huang, P. | Hui, T. | Jancarik, J. | Kim, S H. | Moshinsky, D J. | Rice, A G. | SU9 | Atp-binding | Cell cycle | Cell division | Inhibitor | Mitosis | Phosphorylation | Serine/threonine protein kinase | Su9516 | Transferase
