1ydr
From Proteopedia
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'''STRUCTURE OF CAMP-DEPENDENT PROTEIN KINASE, ALPHA-CATALYTIC SUBUNIT IN COMPLEX WITH H7 PROTEIN KINASE INHIBITOR 1-(5-ISOQUINOLINESULFONYL)-2-METHYLPIPERAZINE''' | '''STRUCTURE OF CAMP-DEPENDENT PROTEIN KINASE, ALPHA-CATALYTIC SUBUNIT IN COMPLEX WITH H7 PROTEIN KINASE INHIBITOR 1-(5-ISOQUINOLINESULFONYL)-2-METHYLPIPERAZINE''' | ||
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[[Category: Huber, R.]] | [[Category: Huber, R.]] | ||
[[Category: Kinzel, V.]] | [[Category: Kinzel, V.]] | ||
| - | [[Category: | + | [[Category: Atp-binding]] |
| - | [[Category: | + | [[Category: Camp]] |
| - | [[Category: | + | [[Category: Isoquinoline sulfonamide]] |
| - | + | [[Category: Phosphorylation]] | |
| - | [[Category: | + | [[Category: Serine/threonine-protein kinase]] |
| - | [[Category: | + | [[Category: Transferase]] |
| - | [[Category: | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 16:11:55 2008'' |
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| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | |
Revision as of 13:11, 3 May 2008
STRUCTURE OF CAMP-DEPENDENT PROTEIN KINASE, ALPHA-CATALYTIC SUBUNIT IN COMPLEX WITH H7 PROTEIN KINASE INHIBITOR 1-(5-ISOQUINOLINESULFONYL)-2-METHYLPIPERAZINE
Overview
The discovery of several hundred different protein kinases involved in highly diverse cellular signaling pathways is in stark contrast to the much smaller number of known modulators of cell signaling. Of these, the H series protein kinase inhibitors (1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H7), N-[2-(methylamino)ethyl]-5-isoquinolinesulfonamide (H8) N-[2-(p-Bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide (H89)) are frequently used to block signaling pathways in studies of cellular regulation. To elucidate inhibition mechanisms at atomic resolution and to enable structure-based drug design of potential therapeutic modulators of signaling pathways, we determined the crystal structures of corresponding complexes with the cAPK catalytic subunit. Complexes with H7 and H8 (2.2 A) and with H89 (2.3 A) define the binding mode of the isoquinoline-sulfonamide derivatives in the ATP-binding site while demonstrating effects of ligand-induced structural change. Specific interactions between the enzyme and the inhibitors include the isoquinoline ring nitrogen ligating to backbone amide of Val-123 and an inhibitor side chain amide bonding to the backbone carbonyl of Glu-170. The conservation of the ATP-binding site of protein kinases allows evaluation of factors governing general selectivity of these inhibitors among kinases. These results should assist efforts in the design of protein kinase inhibitors with specific properties.
About this Structure
1YDR is a Protein complex structure of sequences from Bos taurus. Full crystallographic information is available from OCA.
Reference
Crystal structures of catalytic subunit of cAMP-dependent protein kinase in complex with isoquinolinesulfonyl protein kinase inhibitors H7, H8, and H89. Structural implications for selectivity., Engh RA, Girod A, Kinzel V, Huber R, Bossemeyer D, J Biol Chem. 1996 Oct 18;271(42):26157-64. PMID:8824261 Page seeded by OCA on Sat May 3 16:11:55 2008
