PDBsum entry 3a61

Transferase

PDB id: 3a61

Contents

Protein chain

254 a.a. *

Ligands

STU

* Residue conservation analysis

PDB id:

3a61

Name:

Transferase

Title:

Crystal structure of unphosphorylated p70s6k1 (form ii)

Structure:

Ribosomal protein s6 kinase beta-1. Chain: a. Fragment: unp residues 75-399. Synonym: ribosomal protein s6 kinase i, s6k1, s6k, 70 kda ribosomal protein s6 kinase 1, p70 s6 kinase alpha, p70(s6k)-alpha, p70-s6k, p70s6k, p70-alpha. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108. Expression_system_cell_line: sf21.

Resolution:

3.43Å R-factor: 0.274 R-free: 0.349

Authors:

T.Sunami,N.Byrne,R.E.Diehl,K.Funabashi,D.L.Hall,M.Ikuta,S.B.Patel, J.M.Shipman,R.F.Smith,I.Takahashi,J.Zugay-Murphy,Y.Iwasawa,K.J.Lumb, S.K.Munshi,S.Sharma

Key ref:

T.Sunami et al. (2010). Structural basis of human p70 ribosomal S6 kinase-1 regulation by activation loop phosphorylation. J Biol Chem, 285, 4587-4594. PubMed id: 19864428

Date:

18-Aug-09 Release date: 27-Oct-09

Protein chain

P23443  (KS6B1_HUMAN) -  Ribosomal protein S6 kinase beta-1 from Homo sapiens

Seq: 525 a.a.

Struc: 254 a.a.

Enzyme reactions

• Enzyme class: E.C.2.7.11.1 - non-specific serine/threonine protein kinase.
• Reaction:
  1. L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H⁺
  2. L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H⁺

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

J Biol Chem 285:4587-4594 (2010)

PubMed id: 19864428

Structural basis of human p70 ribosomal S6 kinase-1 regulation by activation loop phosphorylation.

T.Sunami, N.Byrne, R.E.Diehl, K.Funabashi, D.L.Hall, M.Ikuta, S.B.Patel, J.M.Shipman, R.F.Smith, I.Takahashi, J.Zugay-Murphy, Y.Iwasawa, K.J.Lumb, S.K.Munshi, S.Sharma.

ABSTRACT

p70 ribosomal S6 kinase (p70S6K) is a downstream effector of the mTOR signaling pathway involved in cell proliferation, cell growth, cell-cycle progression, and glucose homeostasis. Multiple phosphorylation events within the catalytic, autoinhibitory, and hydrophobic motif domains contribute to the regulation of p70S6K. We report the crystal structures of the kinase domain of p70S6K1 bound to staurosporine in both the unphosphorylated state and in the 3'-phosphoinositide-dependent kinase-1-phosphorylated state in which Thr-252 of the activation loop is phosphorylated. Unphosphorylated p70S6K1 exists in two crystal forms, one in which the p70S6K1 kinase domain exists as a monomer and the other as a domain-swapped dimer. The crystal structure of the partially activated kinase domain that is phosphorylated within the activation loop reveals conformational ordering of the activation loop that is consistent with a role in activation. The structures offer insights into the structural basis of the 3'-phosphoinositide-dependent kinase-1-induced activation of p70S6K and provide a platform for the rational structure-guided design of specific p70S6K inhibitors.