PDBsum entry 3qa0

Transferase

PDB id: 3qa0

Contents

Protein chains

330 a.a.

Ligands

SO4 ×7

EDO ×5

Waters ×229

PDB id:

3qa0

Name:

Transferase

Title:

Crystal structure of the apo-form of human ck2 alpha at ph 6.5

Structure:

Casein kinase ii subunit alpha. Chain: a, b. Fragment: unp residues 1-336. Synonym: ck2alpha, ck ii alpha. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: csnk2a1, ck2a1. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

2.50Å R-factor: 0.209 R-free: 0.249

Authors:

R.Battistutta,A.Ranchio,E.Papinutto

Key ref:

E.Papinutto et al. (2012). Structural and functional analysis of the flexible regions of the catalytic α-subunit of protein kinase CK2. J Struct Biol, 177, 382-391. PubMed id: 22186626

Date:

10-Jan-11 Release date: 11-Jan-12

Protein chains

P68400  (CSK21_HUMAN) -  Casein kinase II subunit alpha from Homo sapiens

Seq: 391 a.a.

Struc: 330 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 Struct Biol 177:382-391 (2012)

PubMed id: 22186626

Structural and functional analysis of the flexible regions of the catalytic α-subunit of protein kinase CK2.

E.Papinutto, A.Ranchio, G.Lolli, L.A.Pinna, R.Battistutta.

ABSTRACT

CK2 is a Ser/Thr protein kinase essential for cell viability. Its activity is anomalously high in several solid (prostate, mammary gland, lung, kidney and head and neck) and haematological tumours (AML, CML and PML), creating conditions favouring the onset of cancer. Cancer cells become addicted to high levels of CK2 activity and therefore this kinase is a remarkable example of "non-oncogene addiction". CK2 is a validated target for cancer therapy with one inhibitor in phase I clinical trials. Several crystal structures of CK2 are available, many in complex with ATP-competitive inhibitors, showing the presence of regions with remarkable flexibility. We present the structural characterisation of these regions by means of seven new crystal structures, in the apo form and in complex with inhibitors. We confirm previous findings about the unique flexibility of the CK2α catalytic subunit in the hinge/αD region, the p-loop and the β4β5 loop, and show here that there is no clear-cut correlation between the conformations of these flexible zones. Our findings challenge some of the current interpretations on the functional role of these regions and dispute the hypothesis that small ligands stabilize an inactive state. The mobility of the hinge/αD region in the human enzyme is unique among protein kinases, and this can be exploited for the development of more selective ATP-competitive inhibitors. The identification of different ligand binding modes to a secondary site can provide hints for the design of non-ATP-competitive inhibitors targeting the interaction between the α catalytic and the β regulatory subunits.