1z5m
From Proteopedia
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|PDB= 1z5m |SIZE=350|CAPTION= <scene name='initialview01'>1z5m</scene>, resolution 2.17Å | |PDB= 1z5m |SIZE=350|CAPTION= <scene name='initialview01'>1z5m</scene>, resolution 2.17Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand= | + | |LIGAND= <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=LI8:N-(3-{[5-BROMO-2-({3-[(PYRROLIDIN-1-YLCARBONYL)AMINO]PHENYL}AMINO)PYRIMIDIN-4-YL]AMINO}PROPYL)-2,2-DIMETHYLMALONAMIDE'>LI8</scene>, <scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene> |
| - | |ACTIVITY= [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] | + | |ACTIVITY= <span class='plainlinks'>[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] </span> |
|GENE= PDPK1, PDK1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | |GENE= PDPK1, PDK1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[1uu7|1uu7]], [[1uu8|1uu8]], [[1uu9|1uu9]], [[1uvr|1uvr]], [[1h1w|1h1w]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1z5m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1z5m OCA], [http://www.ebi.ac.uk/pdbsum/1z5m PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1z5m RCSB]</span> | ||
}} | }} | ||
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[[Category: Adler, M.]] | [[Category: Adler, M.]] | ||
[[Category: Whitlow, M.]] | [[Category: Whitlow, M.]] | ||
| - | [[Category: CL]] | ||
| - | [[Category: GOL]] | ||
| - | [[Category: LI8]] | ||
| - | [[Category: SO4]] | ||
[[Category: protein inhibitor complex]] | [[Category: protein inhibitor complex]] | ||
[[Category: serine kinase]] | [[Category: serine kinase]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 01:29:21 2008'' |
Revision as of 22:29, 30 March 2008
| |||||||
| , resolution 2.17Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , , , , | ||||||
| Gene: | PDPK1, PDK1 (Homo sapiens) | ||||||
| Activity: | Non-specific serine/threonine protein kinase, with EC number 2.7.11.1 | ||||||
| Related: | 1uu7, 1uu8, 1uu9, 1uvr, 1h1w
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal Structure Of N1-[3-[[5-bromo-2-[[3-[(1-pyrrolidinylcarbonyl)amino]phenyl]amino]-4-pyrimidinyl]amino]propyl]-2,2-dimethylpropanediamide Complexed with Human PDK1
Overview
The phosphoinositide 3-kinase/3-phosphoinositide-dependent kinase 1 (PDK1)/Akt signaling pathway plays a key role in cancer cell growth, survival, and tumor angiogenesis and represents a promising target for anticancer drugs. Here, we describe three potent PDK1 inhibitors, BX-795, BX-912, and BX-320 (IC(50) = 11-30 nm) and their initial biological characterization. The inhibitors blocked PDK1/Akt signaling in tumor cells and inhibited the anchorage-dependent growth of a variety of tumor cell lines in culture or induced apoptosis. A number of cancer cell lines with elevated Akt activity were >30-fold more sensitive to growth inhibition by PDK1 inhibitors in soft agar than on tissue culture plastic, consistent with the cell survival function of the PDK1/Akt signaling pathway, which is particularly important for unattached cells. BX-320 inhibited the growth of LOX melanoma tumors in the lungs of nude mice after injection of tumor cells into the tail vein. The effect of BX-320 on cancer cell growth in vitro and in vivo indicates that PDK1 inhibitors may have clinical utility as anticancer agents.
About this Structure
1Z5M is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Novel small molecule inhibitors of 3-phosphoinositide-dependent kinase-1., Feldman RI, Wu JM, Polokoff MA, Kochanny MJ, Dinter H, Zhu D, Biroc SL, Alicke B, Bryant J, Yuan S, Buckman BO, Lentz D, Ferrer M, Whitlow M, Adler M, Finster S, Chang Z, Arnaiz DO, J Biol Chem. 2005 May 20;280(20):19867-74. Epub 2005 Mar 16. PMID:15772071
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