PDBsum entry 1m2r

Transferase

PDB id: 1m2r

Contents

Protein chain

327 a.a. *

Ligands

MNY

Waters ×205

* Residue conservation analysis

PDB id:

1m2r

Name:

Transferase

Title:

Crystal structure of 5,8-di-amino-1,4-di-hydroxy-anthraquinone/ck2 kinase complex

Structure:

Casein kinase ii, alpha chain. Chain: a. Fragment: catalytic subunit. Synonym: ckii. Engineered: yes

Source:

Zea mays. Organism_taxid: 4577. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.

Resolution:

1.70Å R-factor: 0.190 R-free: 0.216

Authors:

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

Key ref:

E.De Moliner et al. (2003). Inhibition of protein kinase CK2 by anthraquinone-related compounds. A structural insight. J Biol Chem, 278, 1831-1836. PubMed id: 12419810 DOI: 10.1074/jbc.M209367200

Date:

25-Jun-02 Release date: 17-Jun-03

Protein chain

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: 10.1074/jbc.M209367200

J Biol Chem 278:1831-1836 (2003)

PubMed id: 12419810

Inhibition of protein kinase CK2 by anthraquinone-related compounds. A structural insight.

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

ABSTRACT

Protein kinases play key roles in signal transduction and therefore are among the most attractive targets for drug design. The pharmacological aptitude of protein kinase inhibitors is highlighted by the observation that various diseases with special reference to cancer are because of the abnormal expression/activity of individual kinases. The resolution of the three-dimensional structure of the target kinase in complex with inhibitors is often the starting point for the rational design of this kind of drugs, some of which are already in advanced clinical trial or even in clinical practice. Here we present and discuss three new crystal structures of ATP site-directed inhibitors in complex with "casein kinase-2" (CK2), a constitutively active protein kinase implicated in a variety of cellular functions and misfunctions. With the help of theoretical calculations, we disclose some key features underlying the inhibitory efficiency of anthraquinone derivatives, outlining three different binding modes into the active site. In particular, we show that a nitro group in a hydroxyanthraquinone scaffold decreases the inhibitory constants K(i) because of electron-withdrawing and resonance effects that enhance the polarization of hydroxylic substituents in paraposition.

Selected figure(s)

Figure 2.
Fig. 2. Overview of CK2 three-dimensional folding. The ribbon diagram of CK2 in complex with MNA (in ball-and-stick) bound in the ATP binding site between the N- and the C-terminal lobes is shown (gray). The location of the inhibitor DAA is also shown (ball-and-stick in black). On the top right are shown the two different positions of the loop 102-108 in the case of the MNA complex (gray) and DAA (or MNX) complex (black) that correspond to a long b-cell axis (around 59.5 Å) and a short one (around 52.2 Å), respectively.

Figure 4.
Fig. 4. Polar interactions (dotted lines) of MNA , MNX, and DAA when bound to CK2. Distances are reported in angstroms. In the DAA scheme, interactions between ATP and residues Glu-114 and Val-116 are reported for comparison (21).

The above figures are reprinted by permission from the ASBMB: J Biol Chem (2003, 278, 1831-1836) copyright 2003.

Figures were selected by an automated process.