3QBN

Structure of Human Aurora A in Complex with a diaminopyrimidine

Summary for 3QBN

• Entry DOI: 10.2210/pdb3qbn/pdb
• Descriptor: Serine/threonine-protein kinase 6, 5-chloro-N~4~-cyclopropyl-N~2~-[4-(2-methoxyethoxy)phenyl]pyrimidine-2,4-diamine (2 entities in total)
• Functional Keywords: kinase domain, diaminopyrimidine, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm, cytoskeleton, centrosome: O14965
• Total number of polymer chains: 1
• Total formula weight: 32837.01

Authors

Gruetter, C.,Simard, J.R.,Rauh, D. (deposition date: 2011-01-13, release date: 2012-01-18, Last modification date: 2023-09-13)

Primary citation

Tueckmantel, S.,Greul, J.N.,Janning, P.,Brockmeyer, A.,Gruetter, C.,Simard, J.R.,Gutbrod, O.,Beck, M.E.,Tietjen, K.,Rauh, D.,Schreier, P.H.
Identification of Ustilago maydis Aurora kinase as a novel antifungal target.
Acs Chem.Biol., 6:926-933, 2011

PubMed Abstract: Infestation of crops by pathogenic fungi has continued to have a major impact by reducing yield and quality, emphasizing the need to identify new targets and develop new agents to improve methods of crop protection. Here we present Aurora kinase from the phytopathogenic fungus Ustilago maydis as a novel target for N-substituted diaminopyrimidines, a class of small-molecule kinase inhibitors. We show that Aurora kinase is essential in U. maydis and that diaminopyrimidines inhibit its activity in vitro. Furthermore, we observed an overall good correlation between in vitro inhibition of Aurora kinase and growth inhibition of diverse fungi in vivo. In vitro inhibition assays with Ustilago and human Aurora kinases indicate that some compounds of the N-substituted diaminopyrimidine class show specificity for the Ustilago enzyme, thus revealing their potential as selective fungicides.

PubMed: 21671622
DOI: 10.1021/cb200112y

Experimental method

X-RAY DIFFRACTION (3.5 Å)