PDBsum entry 3c9w

Transferase

PDB id: 3c9w

Contents

Protein chains

336 a.a. *

Ligands

HMY ×2

Waters ×257

* Residue conservation analysis

PDB id:

3c9w

Name:

Transferase

Title:

Crystal structure of erk-2 with hypothemycin covalently bound

Structure:

Mitogen-activated protein kinase 1. Chain: a, b. Synonym: extracellular signal-regulated kinase 2, erk-2, mitogen- activated protein kinase 2, map kinase 2, mapk 2, p42-mapk, ert1. Engineered: yes

Source:

Rattus norvegicus. Rat. Organism_taxid: 10116. Gene: erk2. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

2.50Å R-factor: 0.201 R-free: 0.274

Authors:

R.J.Rosenfeld

Key ref:

G.Rastelli et al. (2008). Molecular modeling and crystal structure of ERK2-hypothemycin complexes. J Struct Biol, 164, 18-23. PubMed id: 18571434

Date:

18-Feb-08 Release date: 08-Jul-08

Protein chains

P63086  (MK01_RAT) -  Mitogen-activated protein kinase 1 from Rattus norvegicus

Seq: 358 a.a.

Struc: 336 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

J Struct Biol 164:18-23 (2008)

PubMed id: 18571434

Molecular modeling and crystal structure of ERK2-hypothemycin complexes.

G.Rastelli, R.Rosenfeld, R.Reid, D.V.Santi.

ABSTRACT

Resorcylic acid lactones containing a cis-enone-such as hypothemycin-are susceptible to Michael addition reactions and are potent and specific inhibitors of about 45 of the known Ser/Thr/Tyr protein kinases. These inhibitors bind reversibly, and then form a covalent adduct with a completely conserved cysteine in the ATP binding site of their target kinases. As a paradigm for the structures of the cis-enone resorcylic acid lactone complexes with this subset of kinases, we have modeled the structure of ERK2-hypothemycin reversible and covalent complexes using docking and extended molecular dynamics simulations. Subsequently, we determined the 2.5A resolution crystal structure of the complex that was in excellent accord with the modeled structure. The results were used to discuss structure-activity relationships, and provide a structural template for the development of irreversible inhibitors that complement the ATP binding site of kinases.