PDBsum entry 1j91

Transferase

PDB id: 1j91

Contents

Protein chains

327 a.a. *

Ligands

TBS ×2

Waters ×227

* Residue conservation analysis

PDB id:

1j91

Name:

Transferase

Title:

Crystal structure of z. Mays ck2 kinase alpha subunit in complex with the atp-competitive inhibitor 4,5,6,7-tetrabromobenzotriazole

Structure:

Casein kinase ii, alpha chain. Chain: a, b. Synonym: ck ii, ck2-alpha. Engineered: yes

Source:

Zea mays. Organism_taxid: 4577. Expressed in: escherichia coli. Expression_system_taxid: 562

Resolution:

2.22Å R-factor: 0.205 R-free: 0.268

Authors:

R.Battistutta,E.De Moliner,S.Sarno,G.Zanotti,L.A.Pinna

Key ref:

R.Battistutta et al. (2001). Structural features underlying selective inhibition of protein kinase CK2 by ATP site-directed tetrabromo-2-benzotriazole. Protein Sci, 10, 2200-2206. PubMed id: 11604527 DOI: 10.1110/ps.19601

Date:

23-May-01 Release date: 29-May-02

Protein chains

P28523  (CSK2A_MAIZE) -  Casein kinase II subunit alpha from Zea mays

Seq: 332 a.a.

Struc: 327 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

DOI no: 10.1110/ps.19601

Protein Sci 10:2200-2206 (2001)

PubMed id: 11604527

Structural features underlying selective inhibition of protein kinase CK2 by ATP site-directed tetrabromo-2-benzotriazole.

R.Battistutta, E.De Moliner, S.Sarno, G.Zanotti, L.A.Pinna.

ABSTRACT

Two novel crystal structures of Zea mays protein kinase CK2alpha catalytic subunit, one in complex with the specific inhibitor 4,5,6,7-tetrabromobenzotriazole (TBB) and another in the apo-form, were solved at 2.2 A resolution. These structures were compared with those of the enzyme in presence of ATP and GTP (the natural cosubstrates) and the inhibitor emodin. Interaction of TBB with the active site of CK2alpha is mainly due to van der Waals contacts, with the ligand fitting almost perfectly the cavity. One nitrogen of the five-membered ring interacts with two charged residues, Glu 81 and Lys 68, in the depth of the cavity, through two water molecules. These are buried in the active site and are also generally found in the structures of CK2alpha enzyme analyzed so far, with the exception of the complex with emodin. In the N-terminal lobe, the position of helix alphaC is particularly well preserved in all the structures examined; the Gly-rich loop is displaced from the intermediate position it has in the apo-form and in the presence of the natural cosubstrates (ATP/GTP) to either an upper (with TBB) or a lower position (with emodin). The selectivity of TBB for CK2 appears to be mainly dictated by the reduced size of the active site which in most other protein kinases is too large for making stable interactions with this inhibitor.

Selected figure(s)

Figure 3.
Fig. 3. (A) Two clipped views of the active site showing the inhibitor (as cpk model) fitting the cavity are shown. The molecular surface of the protein is represented as a white mesh. Bromine atoms are in red, carbon atoms in green, and nitrogen atoms in blue. (B) Position of TBB with respect to that of ATP (cyan) and emodin (green) in the catalytic site is shown from different points of view. Inhibitor rings lay practically in the same plane of the purine moiety of the natural cosubstrates (bottom).

The above figure is reprinted by permission from the Protein Society: Protein Sci (2001, 10, 2200-2206) copyright 2001.

Figure was selected by an automated process.