3ztx

From Proteopedia

Jump to: navigation, search

Aurora kinase selective inhibitors identified using a Taxol-induced checkpoint sensitivity screen.

Structural highlights

3ztx is a 4 chain structure with sequence from African clawed frog. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:ZTX
NonStd Res:TPO
Activity:Non-specific serine/threonine protein kinase, with EC number 2.7.11.1
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[AUKBA_XENLA] Serine/threonine-protein kinase component of the chromosomal passenger complex (CPC), a complex that acts as a key regulator of mitosis. The CPC complex has essential functions at the centromere in ensuring correct chromosome alignment and segregation and is required for chromatin-induced microtubule stabilization and spindle assembly. Involved in the bipolar attachment of spindle microtubules to kinetochores and is a key regulator for the onset of cytokinesis during mitosis. Required for central/midzone spindle assembly and cleavage furrow formation. Phosphorylates 'Ser-10' of histone H3 during mitosis.[1] [2] [3] [INCEA_XENLA] Component of the chromosomal passenger complex (CPC), a complex that acts as a key regulator of mitosis. The CPC complex has essential functions at the centromere in ensuring correct chromosome alignment and segregation and is required for chromatin-induced microtubule stabilization and spindle assembly. Probably acts through association with aurkb or aurkc. Seems to bind directly to microtubules.[4] [5]

Publication Abstract from PubMed

The members of the Aurora kinase family play critical roles in the regulation of the cell cycle and mitotic spindle assembly and have been intensively investigated as potential targets for a new class of anticancer drugs. We describe a new highly potent and selective class of Aurora kinase inhibitors discovered using a phenotypic cellular screen. Optimized inhibitors display many of the hallmarks of Aurora inhibition including endoreduplication, polyploidy, and loss of cell viability in cancer cells. Structure-activity relationships with respect to kinome-wide selectivity and guided by an Aurora B co-crystal structure resulted in the identification of key selectivity determinants and discovery of a subseries with selectivity toward Aurora A. A direct comparison of biochemical and cellular profiles with respect to published Aurora inhibitors including VX-680, AZD1152, MLN8054, and a pyrimidine-based compound from Genentech demonstrates that compounds 1 and 3 will become valuable additional pharmacological probes of Aurora-dependent functions.

Selective aurora kinase inhibitors identified using a taxol-induced checkpoint sensitivity screen.,Kwiatkowski N, Deng X, Wang J, Tan L, Villa F, Santaguida S, Huang HC, Mitchison T, Musacchio A, Gray N ACS Chem Biol. 2012 Jan 20;7(1):185-96. Epub 2011 Oct 21. PMID:21992004[6]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

Loading citation details..
Citations
2 reviews cite this structure
Structural features of the protein kinase domain and targeted binding by small-molecule inhibitors.
Arter et al. (2022)
1 more
12 other articles
No citations found

See Also

References

  1. ↑ Bolton MA, Lan W, Powers SE, McCleland ML, Kuang J, Stukenberg PT. Aurora B kinase exists in a complex with survivin and INCENP and its kinase activity is stimulated by survivin binding and phosphorylation. Mol Biol Cell. 2002 Sep;13(9):3064-77. PMID:12221116 doi:10.1091/mbc.E02-02-0092
  2. ↑ Murnion ME, Adams RR, Callister DM, Allis CD, Earnshaw WC, Swedlow JR. Chromatin-associated protein phosphatase 1 regulates aurora-B and histone H3 phosphorylation. J Biol Chem. 2001 Jul 13;276(28):26656-65. Epub 2001 May 11. PMID:11350965 doi:10.1074/jbc.M102288200
  3. ↑ Kelly AE, Sampath SC, Maniar TA, Woo EM, Chait BT, Funabiki H. Chromosomal enrichment and activation of the aurora B pathway are coupled to spatially regulate spindle assembly. Dev Cell. 2007 Jan;12(1):31-43. PMID:17199039 doi:10.1016/j.devcel.2006.11.001
  4. ↑ Bolton MA, Lan W, Powers SE, McCleland ML, Kuang J, Stukenberg PT. Aurora B kinase exists in a complex with survivin and INCENP and its kinase activity is stimulated by survivin binding and phosphorylation. Mol Biol Cell. 2002 Sep;13(9):3064-77. PMID:12221116 doi:10.1091/mbc.E02-02-0092
  5. ↑ Kelly AE, Sampath SC, Maniar TA, Woo EM, Chait BT, Funabiki H. Chromosomal enrichment and activation of the aurora B pathway are coupled to spatially regulate spindle assembly. Dev Cell. 2007 Jan;12(1):31-43. PMID:17199039 doi:10.1016/j.devcel.2006.11.001
  6. ↑ Kwiatkowski N, Deng X, Wang J, Tan L, Villa F, Santaguida S, Huang HC, Mitchison T, Musacchio A, Gray N. Selective aurora kinase inhibitors identified using a taxol-induced checkpoint sensitivity screen. ACS Chem Biol. 2012 Jan 20;7(1):185-96. Epub 2011 Oct 21. PMID:21992004 doi:10.1021/cb200305u

Contents


PDB ID 3ztx

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://proteopedia.org/wiki/index.php/3ztx"
Personal tools