PDBsum entry 5j8h

Metal binding protein/transferase

PDB id: 5j8h

Contents

Protein chains

148 a.a.

27 a.a.

Metals

_CA ×2

PDB id:

5j8h

Name:

Metal binding protein/transferase

Title:

Structure of calmodulin in a complex with a peptide derived from a calmodulin-dependent kinase

Structure:

Calmodulin. Chain: a. Synonym: cam. Engineered: yes. Eukaryotic elongation factor 2 kinase. Chain: b. Fragment: residues 74-100. Synonym: eef-2k,calcium/calmodulin-dependent eukaryotic elongation factor 2 kinase.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: calm1, calm, cam, cam1, calm2, cam2, camb, calm3, calml2, cam3, camc, camiii. Expressed in: escherichia coli. Expression_system_taxid: 469008. Gene: eef2k.

NMR struc:

20 models

Authors:

S.Alphonse,K.Lee,A.Piserchio,C.D.J.Tavares,D.H.Giles,R.M.Wellmann, K.N.Dalby,R.Ghose

Key ref:

K.Lee et al. (2016). Structural Basis for the Recognition of Eukaryotic Elongation Factor 2 Kinase by Calmodulin. Structure, 24, 1441-1451. PubMed id: 27499441

Date:

07-Apr-16 Release date: 07-Sep-16

Protein chain

P0DP23  (CALM1_HUMAN) -  Calmodulin-1 from Homo sapiens

Seq: 149 a.a.

Struc: 148 a.a.

Protein chain

O00418  (EF2K_HUMAN) -  Eukaryotic elongation factor 2 kinase from Homo sapiens

Seq: 725 a.a.

Struc: 27 a.a.

Enzyme reactions

• Enzyme class: Chain B: E.C.2.7.11.20 - [elongation factor 2] kinase.
• Reaction: [translation elongation factor 2] + ATP = [translation elongation factor 2]-phosphate + ADP + H⁺
• Cofactor: Ca(2+)

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

Added reference

Structure 24:1441-1451 (2016)

PubMed id: 27499441

Structural Basis for the Recognition of Eukaryotic Elongation Factor 2 Kinase by Calmodulin.

K.Lee, S.Alphonse, A.Piserchio, C.D.Tavares, D.H.Giles, R.M.Wellmann, K.N.Dalby, R.Ghose.

ABSTRACT

Binding of Ca(2+)-loaded calmodulin (CaM) activates eukaryotic elongation factor 2 kinase (eEF-2K) that phosphorylates eEF-2, its only known cellular target, leading to a decrease in global protein synthesis. Here, using an eEF-2K-derived peptide (eEF-2KCBD) that encodes the region necessary for its CaM-mediated activation, we provide a structural basis for their interaction. The striking feature of this association is the absence of Ca(2+) from the CaM C-lobe sites, even under high Ca(2+) conditions. eEF-2KCBD engages CaM largely through the C lobe of the latter in an anti-parallel 1-5-8 hydrophobic mode reinforced by a pair of unique electrostatic contacts. Sparse interactions of eEF-2KCBD with the CaM N lobe results in persisting inter-lobe mobility. A conserved eEF-2K residue (W85) anchors it to CaM by inserting into a deep hydrophobic cavity within the CaM C lobe. Mutation of this residue (W85S) substantially weakens interactions between full-length eEF-2K and CaM in vitro and reduces eEF-2 phosphorylation in cells.