2YIQ

Structural analysis of checkpoint kinase 2 in complex with inhibitor PV1322

Summary for 2YIQ

• Entry DOI: 10.2210/pdb2yiq/pdb
• Related: 1GXC 2CN5 2CN8 2W0J 2W7X 2WTC 2WTD 2WTI 2WTJ 2XBJ 2XM8 2XM9 2YCF 2YCQ 2YCR 2YCS 2YIR 2YIT
• Descriptor: SERINE/THREONINE-PROTEIN KINASE CHK2, (E)-5-(1-(2-CARBAMIMIDOYLHYDRAZONO)ETHYL)-N-(1H-INDOL-6-YL)-1H-INDOLE-2-CARBOXAMIDE, NITRATE ION, ... (4 entities in total)
• Functional Keywords: transferase
• Biological source: HOMO SAPIENS (HUMAN)
• Cellular location: Isoform 2: Nucleus. Isoform 4: Nucleus. Isoform 7: Nucleus. Isoform 9: Nucleus. Isoform 12: Nucleus. Nucleus, PML body: O96017
• Total number of polymer chains: 1
• Total formula weight: 36997.65

Authors

Lountos, G.T.,Jobson, A.G.,Tropea, J.E.,Self, C.,Zhang, G.,Pommier, Y.,Shoemaker, R.H.,Waugh, D.S. (deposition date: 2011-05-16, release date: 2011-09-07, Last modification date: 2023-12-20)

Primary citation

Lountos, G.T.,Jobson, A.G.,Tropea, J.E.,Self, C.R.,Zhang, G.,Pommier, Y.,Shoemaker, R.H.,Waugh, D.S.
X-Ray Structures of Checkpoint Kinase 2 in Complex with Inhibitors that Target its Gatekeeper-Dependent Hydrophobic Pocket.
FEBS Lett., 585:3245-, 2011

PubMed Abstract: The serine/threonine checkpoint kinase 2 (Chk2) is an attractive molecular target for the development of small molecule inhibitors to treat cancer. Here, we report the rational design of Chk2 inhibitors that target the gatekeeper-dependent hydrophobic pocket located behind the adenine-binding region of the ATP-binding site. These compounds exhibit IC(50) values in the low nanomolar range and are highly selective for Chk2 over Chk1. X-ray crystallography was used to determine the structures of the inhibitors in complex with the catalytic kinase domain of Chk2 to verify their modes of binding.

PubMed: 21907711
DOI: 10.1016/J.FEBSLET.2011.08.050

Experimental method

X-RAY DIFFRACTION (1.89 Å)