PDBsum entry 1vzo

Transferase

PDB id: 1vzo

Contents

Protein chain

319 a.a. *

Ligands

BME

SO4

Waters ×182

* Residue conservation analysis

PDB id:

1vzo

Name:

Transferase

Title:

The structure of the n-terminal kinase domain of msk1 reveals a novel autoinhibitory conformation for a dual kinase protein

Structure:

Ribosomal protein s6 kinase alpha 5. Chain: a. Fragment: n-terminal kinase domain, residues 1-350. Synonym: nuclear mitogen-and-stress-activated kinase-1, msk1, rsk- like protein kinase, 90 kda ribosomal protein s6 kinase 5, rlsk. Engineered: yes. Mutation: yes. Other_details: a covalent b-mercaptoethanol adduct included on cystine a 304

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108. Expression_system_cell_line: sf9.

Resolution:

1.80Å R-factor: 0.208 R-free: 0.242

Authors:

K.J.Smith,P.S.Carter,A.Bridges,P.Horrocks,C.Lewis,G.Pettman,A.Clarke, M.Brown,J.Hughes,M.Wilkinson,B.Bax,A.Reith

Key ref:

K.J.Smith et al. (2004). The structure of MSK1 reveals a novel autoinhibitory conformation for a dual kinase protein. Structure, 12, 1067-1077. PubMed id: 15274926 DOI: 10.1016/j.str.2004.02.040

Date:

21-May-04 Release date: 11-Jun-04

Protein chain

O75582  (KS6A5_HUMAN) -  Ribosomal protein S6 kinase alpha-5 from Homo sapiens

Seq: 802 a.a.

Struc: 319 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: 10.1016/j.str.2004.02.040

Structure 12:1067-1077 (2004)

PubMed id: 15274926

The structure of MSK1 reveals a novel autoinhibitory conformation for a dual kinase protein.

K.J.Smith, P.S.Carter, A.Bridges, P.Horrocks, C.Lewis, G.Pettman, A.Clarke, M.Brown, J.Hughes, M.Wilkinson, B.Bax, A.Reith.

ABSTRACT

Mitogen and stress-activated kinase-1 (MSK1) is a serine/threonine protein kinase that is activated by either p38 or p42ERK MAPKs in response to stress or mitogenic extracellular stimuli. MSK1 belongs to a family of protein kinases that contain two distinct kinase domains in one polypeptide chain. We report the 1.8 A crystal structure of the N-terminal kinase domain of MSK1. The crystal structure reveals a unique inactive conformation with the ATP binding site blocked by the nucleotide binding loop. This inactive conformation is stabilized by the formation of a new three-stranded beta sheet on the N lobe of the kinase domain. The three beta strands come from residues at the N terminus of the kinase domain, what would be the alphaB helix in the active conformation, and the activation loop. The new three-stranded beta sheet occupies a position equivalent to the N terminus of the alphaC helix in active protein kinases.

Selected figure(s)

Figure 3.
Figure 3. Overall Structure of MSK1 and PKA(A) and (B) are ribbon diagrams of MSK1 N-terminal domain, (C) and (D) are ribbon diagrams of PKA (PDB code 1ATP) with AMP-PNP shown as red ball-and-sticks. Views (B) and (D) are of the back of the kinase and are rotated 90° relative to (A) and (C) about the vertical axis. The nucleotide binding loop of MSK1 and PKA is shown in red and the activation loop is shown in blue. The aB helix and aChelix of PKA (residues 75-104) and the equivalent residues in MSK1 (residues 84-115) are shown in orange. The three stranded b sheet motif on the surface on the MSK1 N lobe is clearly visible in (B). The three strands are from the N terminus (green), aBhelix (orange), and the activation loop (blue).

The above figure is reprinted by permission from Cell Press: Structure (2004, 12, 1067-1077) copyright 2004.

Figure was selected by the author.