1uu3: Difference between revisions
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|PDB= 1uu3 |SIZE=350|CAPTION= <scene name='initialview01'>1uu3</scene>, resolution 1.70Å | |PDB= 1uu3 |SIZE=350|CAPTION= <scene name='initialview01'>1uu3</scene>, resolution 1.70Å | ||
|SITE= <scene name='pdbsite=AC1:Ly4+Binding+Site+For+Chain+A'>AC1</scene> | |SITE= <scene name='pdbsite=AC1:Ly4+Binding+Site+For+Chain+A'>AC1</scene> | ||
|LIGAND= <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=LY4:(9R)-9-[(DIMETHYLAMINO)METHYL]-6,7,10,11-TETRAHYDRO-9H,18H-5,21 | |LIGAND= <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=LY4:(9R)-9-[(DIMETHYLAMINO)METHYL]-6,7,10,11-TETRAHYDRO-9H,18H-5,21:12,17-DIMETHENODIBENZO[E,K]PYRROLO[3,4-H][1,4,13]OXADIAZACYCLOHEXADECINE-18,20-DIONE'>LY4</scene> and <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene> | ||
|ACTIVITY= [http://en.wikipedia.org/wiki/Transferred_entry:_2.7.11.1 Transferred entry: 2.7.11.1], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.37 2.7.1.37] | |ACTIVITY= [http://en.wikipedia.org/wiki/Transferred_entry:_2.7.11.1 Transferred entry: 2.7.11.1], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.37 2.7.1.37] | ||
|GENE= | |GENE= | ||
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[[Category: transferase]] | [[Category: transferase]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 23 13:54:53 2008'' | ||
Revision as of 14:54, 23 March 2008
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| , resolution 1.70Å | |||||||
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| Ligands: | , and | ||||||
| Activity: | Transferred entry: 2.7.11.1, with EC number 2.7.1.37 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
STRUCTURE OF HUMAN PDK1 KINASE DOMAIN IN COMPLEX WITH LY333531
OverviewOverview
LY333531, BIM-1, BIM-2, BIM-3, and BIM-8 are bisindolyl maleimide-based, nanomolar protein kinase C inhibitors. LY333531, a PKCbeta-specific inhibitor, is in clinical trials against diabetes and cardiac ventricular hypertrophy complications. Specificity analysis with a panel of 29 protein kinases reveals that these bisindolyl maleimide inhibitors also inhibit PDK1, a key kinase from the insulin signaling pathway, albeit in the lower microM range. To understand the molecular basis of inhibition, the PDK1 kinase domain was cocrystallized with these bisindolyl maleimide inhibitors. The inhibitor complexes represent the first structural description of this class of compounds, revealing their unusual nonplanar conformation within the ATP binding site and also explaining the higher inhibitory potential of LY33331 compared to the BIM compounds toward PDK1. A combination of site-directed mutagenesis and essential dynamics analysis gives further insight into PDK1 and also PKC inhibition by these compounds, and may aid inhibitor design.
About this StructureAbout this Structure
1UU3 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
Interactions of LY333531 and other bisindolyl maleimide inhibitors with PDK1., Komander D, Kular GS, Schuttelkopf AW, Deak M, Prakash KR, Bain J, Elliott M, Garrido-Franco M, Kozikowski AP, Alessi DR, van Aalten DM, Structure. 2004 Feb;12(2):215-26. PMID:14962382
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Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)
OCA- Pages with broken file links
- Homo sapiens
- Single protein
- Transferred entry: 2 7.11 1
- Aalten, D M.F Van.
- Alessi, D R.
- Bain, J.
- Deak, M.
- Elliot, M.
- Garrido-Franco, M.
- Komander, D.
- Kozikowski, A P.
- Kular, G S.
- Prakash, K R.
- Schuttelkopf, A W.
- GOL
- LY4
- SO4
- Cancer
- Diabetes
- Inhibitor
- Ly333531
- Pdk1
- Pkb
- Protein kinase
- Serine/threonine-protein kinase
- Transferase