PDBsum entry 3kk8

Transferase

PDB id: 3kk8

Contents

Protein chain

284 a.a. *

Metals

_MG

Waters ×227

* Residue conservation analysis

PDB id:

3kk8

Name:

Transferase

Title:

Camkii substrate complex a

Structure:

Calcium/calmodulin dependent protein kinase ii. Chain: a. Fragment: camkii kinase domain. Engineered: yes

Source:

Caenorhabditis elegans. Nematode. Organism_taxid: 6239. Gene: unc-43, k11e8.1, k11e8.1d. Expressed in: escherichia coli. Expression_system_taxid: 562

Resolution:

1.72Å R-factor: 0.179 R-free: 0.216

Authors:

J.Kuriyan,L.H.Chao,P.Pellicena,S.Deindl,L.A.Barclay,H.Schulman

Key ref:

L.H.Chao et al. (2010). Intersubunit capture of regulatory segments is a component of cooperative CaMKII activation. Nat Struct Biol, 17, 264-272. PubMed id: 20139983

Date:

04-Nov-09 Release date: 09-Feb-10

Protein chain

O62305  (KCC2D_CAEEL) -  Calcium/calmodulin-dependent protein kinase type II from Caenorhabditis elegans

Seq: 720 a.a.

Struc: 284 a.a.*

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

Enzyme reactions

• Enzyme class: E.C.2.7.11.17 - calcium/calmodulin-dependent 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⁺
• Cofactor: Ca(2+)

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

reference

Nat Struct Biol 17:264-272 (2010)

PubMed id: 20139983

Intersubunit capture of regulatory segments is a component of cooperative CaMKII activation.

L.H.Chao, P.Pellicena, S.Deindl, L.A.Barclay, H.Schulman, J.Kuriyan.

ABSTRACT

The dodecameric holoenzyme of calcium-calmodulin-dependent protein kinase II (CaMKII) responds to high-frequency Ca(2+) pulses to become Ca(2+) independent. A simple coincidence-detector model for Ca(2+)-frequency dependency assumes noncooperative activation of kinase domains. We show that activation of CaMKII by Ca(2+)-calmodulin is cooperative, with a Hill coefficient of approximately 3.0, implying sequential kinase-domain activation beyond dimeric units. We present data for a model in which cooperative activation includes the intersubunit 'capture' of regulatory segments. Such a capture interaction is seen in a crystal structure that shows extensive contacts between the regulatory segment of one kinase and the catalytic domain of another. These interactions are mimicked by a natural inhibitor of CaMKII. Our results show that a simple coincidence-detection model cannot be operative and point to the importance of kinetic dissection of the frequency-response mechanism in future experiments.