PDBsum entry 3c5u

Transferase

PDB id: 3c5u

Contents

Protein chain

338 a.a. *

Ligands

P41 ×2

Waters ×76

* Residue conservation analysis

PDB id:

3c5u

Name:

Transferase

Title:

P38 alpha map kinase complexed with a benzothiazole based inhibitor

Structure:

Mitogen-activated protein kinase 14. Chain: a. Synonym: mitogen-activated protein kinase p38 alpha, map kinase p38 alpha, cytokine suppressive anti-inflammatory drug-binding protein, csaid-binding protein, csbp, max-interacting protein 2, map kinase mxi2, sapk2a. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: mapk14, csbp, csbp1, csbp2, cspb1, mxi2. Expressed in: escherichia coli. Expression_system_taxid: 562. Expression_system_cell_line: bl21 de3.

Resolution:

2.80Å R-factor: 0.263 R-free: 0.296

Authors:

J.S.Sack

Key ref:

C.Liu et al. (2008). Benzothiazole based inhibitors of p38alpha MAP kinase. Bioorg Med Chem Lett, 18, 1874-1879. PubMed id: 18296051 DOI: 10.1016/j.bmcl.2008.02.011

Date:

01-Feb-08 Release date: 25-Mar-08

Protein chain

Q16539  (MK14_HUMAN) -  Mitogen-activated protein kinase 14 from Homo sapiens

Seq: 360 a.a.

Struc: 338 a.a.

Enzyme reactions

• Enzyme class: E.C.2.7.11.24 - mitogen-activated 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: 10.1016/j.bmcl.2008.02.011

Bioorg Med Chem Lett 18:1874-1879 (2008)

PubMed id: 18296051

Benzothiazole based inhibitors of p38alpha MAP kinase.

C.Liu, J.Lin, S.Pitt, R.F.Zhang, J.S.Sack, S.E.Kiefer, K.Kish, A.M.Doweyko, H.Zhang, P.H.Marathe, J.Trzaskos, M.Mckinnon, J.H.Dodd, J.C.Barrish, G.L.Schieven, K.Leftheris.

ABSTRACT

Rational design, synthesis, and SAR studies of a novel class of benzothiazole based inhibitors of p38alpha MAP kinase are described. The issue of metabolic instability associated with vicinal phenyl, benzo[d]thiazol-6-yl oxazoles/imidazoles was addressed by the replacement of the central oxazole or imidazole ring with an aminopyrazole system. The proposed binding mode of this new class of p38alpha inhibitors was confirmed by X-ray crystallographic studies of a representative inhibitor (6a) bound to the p38alpha enzyme.