2Z7Q

Crystal structure of the N-terminal kinase domain of human RSK-1 bound to AMP-PCP

Summary for 2Z7Q

• Entry DOI: 10.2210/pdb2z7q/pdb
• Related: 2Z7R 2Z7S
• Descriptor: Ribosomal protein S6 kinase alpha-1, MAGNESIUM ION, PHOSPHOMETHYLPHOSPHONIC ACID ADENYLATE ESTER, ... (4 entities in total)
• Functional Keywords: protein kinase; cancer; kinase inhibitor, atp-binding, magnesium, metal-binding, nucleotide-binding, phosphorylation, serine/threonine-protein kinase, transferase
• Biological source: Homo sapiens (human)
• Cellular location: Nucleus: Q15418
• Total number of polymer chains: 1
• Total formula weight: 37306.90

Authors

Ikuta, M.,Munshi, S.K. (deposition date: 2007-08-28, release date: 2008-05-13, Last modification date: 2023-11-01)

Primary citation

Ikuta, M.,Kornienko, M.,Byrne, N.,Reid, J.C.,Mizuarai, S.,Kotani, H.,Munshi, S.K.
Crystal structures of the N-terminal kinase domain of human RSK1 bound to three different ligands: Implications for the design of RSK1 specific inhibitors.
Protein Sci., 16:2626-2635, 2007

PubMed Abstract: The p90 ribosomal S6 kinases (RSKs) also known as MAPKAP-Ks are serine/threonine protein kinases that are activated by ERK or PDK1 and act as downstream effectors of mitogen-activated protein kinase (MAPK). RSK1, a member of the RSK family, contains two distinct kinase domains in a single polypeptide chain, the regulatory C-terminal kinase domain (CTKD) and the catalytic N-terminal kinase domain (NTKD). Autophosphorylation of the CTKD leads to activation of the NTKD that subsequently phosphorylates downstream substrates. Here we report the crystal structures of the unactivated RSK1 NTKD bound to different ligands at 2.0 A resolution. The activation loop and helix alphaC, key regulatory elements of kinase function, are disordered. The DFG motif of the inactive RSK1 adopts an "active-like" conformation. The beta-PO(4) group in the AMP-PCP complex adopts a unique conformation that may contribute to inactivity of the enzyme. Structures of RSK1 ligand complexes offer insights into the design of novel anticancer agents and into the regulation of the catalytic activity of RSKs.

PubMed: 17965187
DOI: 10.1110/ps.073123707

Experimental method

X-RAY DIFFRACTION (2 Å)