PDBsum entry 3fpm

Transferase

PDB id: 3fpm

Contents

Protein chain

283 a.a. *

Ligands

793

* Residue conservation analysis

PDB id:

3fpm

Name:

Transferase

Title:

Crystal structure of a squarate inhibitor bound to mapkap kinase-2

Structure:

Map kinase-activated protein kinase 2. Chain: a. Fragment: protein kinase domain. Synonym: mapk-activated protein kinase 2, mapkap kinase 2, mapkapk-2, mk2. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: mapkapk2. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

3.30Å R-factor: 0.284 R-free: 0.337

Authors:

K.D.Parris

Key ref:

F.Lovering et al. (2009). Identification and SAR of squarate inhibitors of mitogen activated protein kinase-activated protein kinase 2 (MK-2). Bioorg Med Chem Lett, 17, 3342-3351. PubMed id: 19364658

Date:

05-Jan-09 Release date: 07-Apr-09

Protein chain

P49137  (MAPK2_HUMAN) -  MAP kinase-activated protein kinase 2 from Homo sapiens

Seq: 400 a.a.

Struc: 283 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

Bioorg Med Chem Lett 17:3342-3351 (2009)

PubMed id: 19364658

Identification and SAR of squarate inhibitors of mitogen activated protein kinase-activated protein kinase 2 (MK-2).

F.Lovering, S.Kirincich, W.Wang, K.Combs, L.Resnick, J.E.Sabalski, J.Butera, J.Liu, K.Parris, J.B.Telliez.

ABSTRACT

A novel series of inhibitors for mitogen activated protein kinase-activated protein kinase 2 (MK-2) are reported. These squarate based inhibitors were identified via a high-throughput screen. An MK2 co-structure with the starting ligand was obtained and a structure based approach was followed to optimize potency and selectivity.