PDBsum entry 2qr7

Transferase

PDB id: 2qr7

Contents

Protein chain

298 a.a. *

Metals

_NA

Waters ×91

* Residue conservation analysis

PDB id:

2qr7

Name:

Transferase

Title:

2.0a x-ray structure of c-terminal kinase domain of p90 ribosomal s6 kinase 2: se-met derivative

Structure:

Ribosomal protein s6 kinase alpha-3. Chain: a. Synonym: s6k-alpha 3, 90 kda ribosomal protein s6 kinase 3, p90-rsk 3, ribosomal s6 kinase 2, rsk-2, pp90rsk2, map kinase-activated protein kinase 1b, mapkapk1b. Engineered: yes. Mutation: yes

Source:

Mus musculus. House mouse. Organism_taxid: 10090. Gene: rps6ka3, rps6ka-rs1, rsk2. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

2.00Å R-factor: 0.205 R-free: 0.238

Authors:

M.Malakhova,V.Tereshko,Z.Dong

Key ref:

M.Malakhova et al. (2008). Structural basis for activation of the autoinhibitory C-terminal kinase domain of p90 RSK2. Nat Struct Mol Biol, 15, 112-113. PubMed id: 18084304 DOI: 10.1038/nsmb1347

Date:

27-Jul-07 Release date: 11-Dec-07

Protein chain

P18654  (KS6A3_MOUSE) -  Ribosomal protein S6 kinase alpha-3 from Mus musculus

Seq: 740 a.a.

Struc: 298 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

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

DOI no: 10.1038/nsmb1347

Nat Struct Mol Biol 15:112-113 (2008)

PubMed id: 18084304

Structural basis for activation of the autoinhibitory C-terminal kinase domain of p90 RSK2.

M.Malakhova, V.Tereshko, S.Y.Lee, K.Yao, Y.Y.Cho, A.Bode, Z.Dong.

ABSTRACT

The X-ray structure at 2.0-A resolution of the p90 ribosomal S6 kinase 2 C-terminal kinase domain revealed a C-terminal autoinhibitory alphaL-helix that was embedded in the kinase scaffold and determines the inactive kinase conformation. We suggest a mechanism of activation through displacement of the alphaL-helix and rearrangement of the conserved residue Glu500, as well as the reorganization of the T-loop into the active conformation.

Selected figure(s)

Figure 1.
The autoinhibitory C-terminal L-helix is shown in yellow. (a) The folding diagram. Disordered residues 715–740 are indicated in gray. (b) The 'cradle' position of the L-helix on the potential surface (positive in blue, negative in red). See Supplementary Methods and Supplementary Table 1 online for details of the structure determination and crystallographic statistics, respectively. The sequence alignment is shown in Supplementary Figure 4 online.

Figure 2.
(a) The CTD superimposed on active PKA (chain A from PDB 1CDK) illustrates the different positions of the D-helix. Boxed region corresponds to boxed region in c. The ligand (inhibitory peptide, purple ribbon) and an ATP analog (AMP-PNP; blue van der Waals surface representation) bound to PKA are included. (b) The CTD RSK2 superimposed on the autoinhibited Ca^2+/calmodulin-dependent protein kinase I (PDB 1A06). (c) A comparison of the active sites of CTD and PKA. Selected RSK2 CTD residues are shown. Only residue Glu127 (analogous to Glu500 in the CTD structure), which differs in the two structures, is shown for PKA. The ATP analog and Mg^2+ ions (balls) are shown in blue.

The above figures are reprinted by permission from Macmillan Publishers Ltd: Nat Struct Mol Biol (2008, 15, 112-113) copyright 2008.