PDBsum entry 2gcd

Transferase

PDB id: 2gcd

Contents

Protein chains

309 a.a. *

Ligands

STU ×2

Waters ×277

* Residue conservation analysis

PDB id:

2gcd

Name:

Transferase

Title:

Tao2 kinase domain-staurosporine structure

Structure:

Serine/threonine-protein kinase tao2. Chain: a, b. Synonym: thousand and one amino acid protein 2. Engineered: yes

Source:

Rattus norvegicus. Norway rat. Organism_taxid: 10116. Gene: tao2. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108

Resolution:

2.55Å R-factor: 0.203 R-free: 0.261

Authors:

T.Zhou,L.Sun,Y.Gao,S.Earnest,M.H.Cobb,E.J.Goldsmith

Key ref:

T.J.Zhou et al. (2006). Crystal structure of the MAP3K TAO2 kinase domain bound by an inhibitor staurosporine. Acta Biochim Biophys Sin (shanghai), 38, 385-392. PubMed id: 16761096

Date:

14-Mar-06 Release date: 05-Sep-06

Protein chains

Q9JLS3  (TAOK2_RAT) -  Serine/threonine-protein kinase TAO2 from Rattus norvegicus

Seq: 1235 a.a.

Struc: 309 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

Acta Biochim Biophys Sin (shanghai) 38:385-392 (2006)

PubMed id: 16761096

Crystal structure of the MAP3K TAO2 kinase domain bound by an inhibitor staurosporine.

T.J.Zhou, L.G.Sun, Y.Gao, E.J.Goldsmith.

ABSTRACT

Mitogen-activated protein kinase (MAPK) signal transduction pathways are ubiquitous in eukaryotic cells, which transfer signals from the cell surface to the nucleus, controlling multiple cellular programs. MAPKs are activated by MAPK kinases [MAP2Ks or MAP/extracellular signal-regulated kinase (ERK) kinases (MEK)], which in turn are activated by MAPK kinase kinases (MAP3Ks). TAO2 is a MAP3K level kinase that activates the MAP2Ks MEK3 and MEK6 to activate p38 MAPKs. Because p38 MAPKs are key regulators of expression of inflammatory cytokines, they appear to be involved in human diseases such as asthma and autoimmunity. As an upstream activator of p38s, TAO2 represents a potential drug target. Here we report the crystal structure of active TAO2 kinase domain in complex with staurosporine, a broad-range protein kinase inhibitor that inhibits TAO2 with an IC50 of 3 mM. The structure reveals that staurosporine occupies the position where the adenosine of ATP binds in TAO2, and the binding of the inhibitor mimics many features of ATP binding. Both polar and nonpolar interactions contribute to the enzyme-inhibitor recognition. Staurosporine induces conformational changes in TAO2 residues that surround the inhibitor molecule, but causes very limited global changes in the kinase. The structure provides atomic details for TAO2-staurosporine interactions, and explains the relatively low potency of staurosporine against TAO2. The structure presented here should aid in the design of inhibitors specific to TAO2 and related kinases.