PDBsum entry 2o5k

Transferase

PDB id

2o5k

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Contents

			Protein chain

					350 a.a. *

			Ligands

					HBM

* Residue conservation analysis

PDB id:

2o5k

Links

Name:

Transferase

Title:

Crystal structure of gsk3beta in complex with a benzoimidazol inhibitor

Structure:

Glycogen synthase kinase-3 beta. Chain: a. Fragment: residues 22-393. Synonym: gsk-3 beta. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli bl21. Expression_system_taxid: 511693.

Resolution:

3.20Å

R-factor:

0.240

R-free:

0.309

Authors:

D.Shin,S.C.Lee,Y.S.Heo,Y.S.Cho,Y.E.Kim,Y.L.Hyun,J.M.Cho,Y.S.Lee,S.Ro

Key ref:

D.Shin et al. (2007). Design and synthesis of 7-hydroxy-1H-benzoimidazole derivatives as novel inhibitors of glycogen synthase kinase-3beta. Bioorg Med Chem Lett, 17, 5686-5689. PubMed id: 17764934 DOI: 10.1016/j.bmcl.2007.07.056

Date:

06-Dec-06

Release date:

23-Oct-07

PROCHECK

	Headers

	References

Protein chain

P49841 (GSK3B_HUMAN) - Glycogen synthase kinase-3 beta from Homo sapiens

Seq: Struc:					420 a.a. 350 a.a.

Key:

PfamA domain

Secondary structure

CATH domain



		Enzyme reactions

Enzyme class:

E.C.2.7.11.26 - [tau protein] kinase.

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

Reaction:

1.	L-seryl-[tau protein] + ATP = O-phospho-L-seryl-[tau protein] + ADP + H⁺
2.	L-threonyl-[tau protein] + ATP = O-phospho-L-threonyl-[tau protein] + ADP + H⁺

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

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

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

reference

DOI no: 10.1016/j.bmcl.2007.07.056	Bioorg Med Chem Lett 17:5686-5689 (2007)
PubMed id: 17764934

Design and synthesis of 7-hydroxy-1H-benzoimidazole derivatives as novel inhibitors of glycogen synthase kinase-3beta.
D.Shin, S.C.Lee, Y.S.Heo, W.Y.Lee, Y.S.Cho, Y.E.Kim, Y.L.Hyun, J.M.Cho, Y.S.Lee, S.Ro.

ABSTRACT

A hydroxy functional group was introduced as the hydrogen bond donor and acceptor at the hinge region of protein kinase in order to develop novel ATP-competitive inhibitors. Several derivatives of 7-hydroxyl-1H-benzoimidazole were designed as inhibitors of glycogen synthase kinase-3beta with the help of ab initio calculations and a docking study. Enzymatic assay and an X-ray complex study showed that these designed compounds were highly potent ATP-competitive inhibitors.

Literature references that cite this PDB file's key reference

PubMed id

Reference

21212533

K.Saeki, M.Machida, Y.Kinoshita, R.Takasawa, and S.Tanuma (2011).
Glycogen synthase kinase-3β2 has lower phosphorylation activity to tau than glycogen synthase kinase-3β1.

Biol Pharm Bull, 34, 146-149.

19366350

G.V.Rayasam, V.K.Tulasi, R.Sodhi, J.A.Davis, and A.Ray (2009).
Glycogen synthase kinase 3: more than a namesake.

Br J Pharmacol, 156, 885-898.

19440740

K.H.Kim, I.Gaisina, F.Gallier, D.Holzle, S.Y.Blond, A.Mesecar, and A.P.Kozikowski (2009).
Use of molecular modeling, docking, and 3D-QSAR studies for the determination of the binding mode of benzofuran-3-yl-(indol-3-yl)maleimides as GSK-3beta inhibitors.

J Mol Model, 15, 1463-1479.

18855890

M.L.Mohler, Y.He, Z.Wu, D.J.Hwang, and D.D.Miller (2009).
Recent and emerging anti-diabetes targets.

Med Res Rev, 29, 125-195.

19475596

S.Kruggel, and T.Lemcke (2009).
Generation and evaluation of a homology model of PfGSK-3.

Arch Pharm (Weinheim), 342, 327-332.

18851699

A.Kannoji, S.Phukan, V.Sudher Babu, and V.N.Balaji (2008).
GSK3beta: a master switch and a promising target.

Expert Opin Ther Targets, 12, 1443-1455.

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.