PDBsum entry 1zoh

Transferase

PDB id

1zoh

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Contents

			Protein chain

					326 a.a. *

			Ligands

					K44


					EDO

			Metals

					_NA


					_CL ×2

			Waters ×379

* Residue conservation analysis

PDB id:

1zoh

Links

Name:

Transferase

Title:

Crystal structure of protein kinase ck2 in complex with tbb- derivatives inhibitors

Structure:

Protein kinase ck2, alpha subunit. Chain: a. Synonym: ck ii, ck2-alpha. Engineered: yes

Source:

Zea mays. Organism_taxid: 4577. Gene: ack2. Expressed in: escherichia coli. Expression_system_taxid: 562

Resolution:

1.81Å

R-factor:

0.165

R-free:

0.221

Authors:

R.Battistutta,M.Mazzorana,S.Sarno,Z.Kazimierczuk,G.Zanotti,L.A.Pinna

Key ref:

R.Battistutta et al. (2005). Inspecting the structure-activity relationship of protein kinase CK2 inhibitors derived from tetrabromo-benzimidazole. Chem Biol, 12, 1211-1219. PubMed id: 16298300 DOI: 10.1016/j.chembiol.2005.08.015

Date:

13-May-05

Release date:

29-Nov-05

PROCHECK

	Headers

	References

Protein chain

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

Seq: Struc:					332 a.a. 326 a.a.

Key:

PfamA domain

Secondary structure

CATH domain



		Enzyme reactions

Enzyme class:

E.C.2.7.11.1 - non-specific serine/threonine protein kinase.

[IntEnz] [ExPASy] [KEGG] [BRENDA]

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⁺

L-seryl-[protein]	+	ATP	=	O-phospho-L-seryl-[protein]	+	ADP	+	H(+)

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: 10.1016/j.chembiol.2005.08.015	Chem Biol 12:1211-1219 (2005)
PubMed id: 16298300

Inspecting the structure-activity relationship of protein kinase CK2 inhibitors derived from tetrabromo-benzimidazole.
R.Battistutta, M.Mazzorana, S.Sarno, Z.Kazimierczuk, G.Zanotti, L.A.Pinna.

ABSTRACT

CK2 is a very pleiotropic protein kinase whose high constitutive activity is suspected to cooperate to neoplasia. Here, the crystal structure of the complexes between CK2 and three selective tetrabromo-benzimidazole derivatives inhibiting CK2 with Ki values between 40 and 400 nM are presented. The ligands bind to the CK2 active site in a different way with respect to the parent compound TBB. They enter more deeply into the cavity, establishing halogen bonds with the backbone of Glu114 and Val116 in the hinge region. A detailed analysis of the interactions highlights a major role of the hydrophobic effect in establishing the rank of potency within this class of inhibitors and shows that polar interactions are responsible for the different orientation of the molecules in the active site.

Selected figure(s)



	Figure 4. Figure 4. K44 Interactions		Figure 5. Figure 5. Stereo Representation of the Main Hydrophobic Residues Surrounding the Inhibitors in the ATP Binding Pocket

Figures were selected by an automated process.

Literature references that cite this PDB file's key reference

PubMed id

Reference

21276940

O.Fedorov, K.Huber, A.Eisenreich, P.Filippakopoulos, O.King, A.N.Bullock, D.Szklarczyk, L.J.Jensen, D.Fabbro, J.Trappe, U.Rauch, F.Bracher, and S.Knapp (2011).
Specific CLK inhibitors from a novel chemotype for regulation of alternative splicing.

Chem Biol, 18, 67-76.

PDB codes:

2vag 2wu6 2wu7

21290074

W.Zierkiewicz, R.Wieczorek, P.Hobza, and D.Michalska (2011).
Halogen bonded complexes between volatile anaesthetics (chloroform, halothane, enflurane, isoflurane) and formaldehyde: a theoretical study.

Phys Chem Chem Phys, 13, 5105-5113.

19526464

G.Cozza, A.Bortolato, and S.Moro (2010).
How druggable is protein kinase CK2?

Med Res Rev, 30, 419-462.

20198231

H.D.Arman, R.L.Gieseking, T.W.Hanks, and W.T.Pennington (2010).
Complementary halogen and hydrogen bonding: sulfur...iodine interactions and thioamide ribbons.

Chem Commun (Camb), 46, 1854-1856.

19821123

N.Zhang, and R.Zhong (2010).
Structural basis for decreased affinity of Emodin binding to Val66-mutated human CK2 alpha as determined by molecular dynamics.

J Mol Model, 16, 771-780.

20851342

S.Baumli, J.A.Endicott, and L.N.Johnson (2010).
Halogen bonds form the basis for selective P-TEFb inhibition by DRB.

Chem Biol, 17, 931-936.

PDB codes:

3my1 3my5

20428531

Y.Lu, Y.Wang, and W.Zhu (2010).
Nonbonding interactions of organic halogens in biological systems: implications for drug discovery and biomolecular design.

Phys Chem Chem Phys, 12, 4543-4551.

18563535

R.Prudent, V.Moucadel, M.López-Ramos, S.Aci, B.Laudet, L.Mouawad, C.Barette, J.Einhorn, C.Einhorn, J.N.Denis, G.Bisson, F.Schmidt, S.Roy, L.Lafanechere, J.C.Florent, and C.Cochet (2008).
Expanding the chemical diversity of CK2 inhibitors.

Mol Cell Biochem, 316, 71-85.

18704226

S.Sarno, and L.A.Pinna (2008).
Protein kinase CK2 as a druggable target.

Mol Biosyst, 4, 889-894.

17133643

M.A.Pagano, G.Poletto, G.Di Maira, G.Cozza, M.Ruzzene, S.Sarno, J.Bain, M.Elliott, S.Moro, G.Zagotto, F.Meggio, and L.A.Pinna (2007).
Tetrabromocinnamic acid (TBCA) and related compounds represent a new class of specific protein kinase CK2 inhibitors.

Chembiochem, 8, 129-139.

17768728

R.Battistutta, M.Mazzorana, L.Cendron, A.Bortolato, S.Sarno, Z.Kazimierczuk, G.Zanotti, S.Moro, and L.A.Pinna (2007).
The ATP-binding site of protein kinase CK2 holds a positive electrostatic area and conserved water molecules.

Chembiochem, 8, 1804-1809.

PDB codes:

2oxd 2oxx 2oxy

The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.