4NEU

X-ray structure of Receptor Interacting Protein 1 (RIP1)kinase domain with a 1-aminoisoquinoline inhibitor

Summary for 4NEU

• Entry DOI: 10.2210/pdb4neu/pdb
• Descriptor: Receptor-interacting serine/threonine-protein kinase 1, MAGNESIUM ION, 1-[4-(1-aminoisoquinolin-5-yl)phenyl]-3-(5-tert-butyl-1,2-oxazol-3-yl)urea, ... (4 entities in total)
• Functional Keywords: kinase, atp binding, phosphorylation, transferase
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm: Q13546
• Total number of polymer chains: 2
• Total formula weight: 77245.26

Authors

Nolte, R.T.,Ward, P.,kahler, K.M.,Campobasso, N. (deposition date: 2013-10-30, release date: 2013-11-20, Last modification date: 2024-02-28)

Primary citation

Harris, P.A.,Bandyopadhyay, D.,Berger, S.B.,Campobasso, N.,Capriotti, C.A.,Cox, J.A.,Dare, L.,Finger, J.N.,Hoffman, S.J.,Kahler, K.M.,Lehr, R.,Lich, J.D.,Nagilla, R.,Nolte, R.T.,Ouellette, M.T.,Pao, C.S.,Schaeffer, M.C.,Smallwood, A.,Sun, H.H.,Swift, B.A.,Totoritis, R.D.,Ward, P.,Marquis, R.W.,Bertin, J.,Gough, P.J.
Discovery of Small Molecule RIP1 Kinase Inhibitors for the Treatment of Pathologies Associated with Necroptosis.
ACS Med Chem Lett, 4:1238-1243, 2013

PubMed Abstract: Potent inhibitors of RIP1 kinase from three distinct series, 1-aminoisoquinolines, pyrrolo[2,3-b]pyridines, and furo[2,3-d]pyrimidines, all of the type II class recognizing a DLG-out inactive conformation, were identified from screening of our in-house kinase focused sets. An exemplar from the furo[2,3-d]pyrimidine series showed a dose proportional response in protection from hypothermia in a mouse model of TNFα induced lethal shock.

PubMed: 24900635
DOI: 10.1021/ml400382p

Experimental method

X-RAY DIFFRACTION (2.57 Å)