PDBsum entry 3bwj

Transferase/transferase inhibitor

PDB id: 3bwj

Contents

Protein chain

341 a.a. *

Ligands

ARX ×2

Waters ×175

* Residue conservation analysis

PDB id:

3bwj

Name:

Transferase/transferase inhibitor

Title:

Complex of pka with the bisubstrate protein kinase inhibitor lead compound arc-1034

Structure:

Camp-dependent protein kinase, alpha-catalytic subunit. Chain: a. Synonym: pka c-alpha. Engineered: yes

Source:

Bos taurus. Bovine. Organism_taxid: 9913. Gene: prkaca. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

2.30Å R-factor: 0.201 R-free: 0.249

Authors:

D.Lavogina,N.Koenig,A.Uri,D.Bossemeyer

Key ref:

D.Lavogina et al. (2009). Structural analysis of ARC-type inhibitor (ARC-1034) binding to protein kinase A catalytic subunit and rational design of bisubstrate analogue inhibitors of basophilic protein kinases. J Med Chem, 52, 308-321. PubMed id: 19143565

Date:

09-Jan-08 Release date: 03-Feb-09

Protein chain

P00517  (KAPCA_BOVIN) -  cAMP-dependent protein kinase catalytic subunit alpha from Bos taurus

Seq: 351 a.a.

Struc: 341 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class: E.C.2.7.11.11 - cAMP-dependent 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 Med Chem 52:308-321 (2009)

PubMed id: 19143565

Structural analysis of ARC-type inhibitor (ARC-1034) binding to protein kinase A catalytic subunit and rational design of bisubstrate analogue inhibitors of basophilic protein kinases.

D.Lavogina, M.Lust, I.Viil, N.König, G.Raidaru, J.Rogozina, E.Enkvist, A.Uri, D.Bossemeyer.

ABSTRACT

The crystal structure of a complex of the catalytic subunit (type alpha) of cAMP-dependent protein kinase (PKA C alpha) with ARC-type inhibitor (ARC-1034), the presumed lead scaffold of previously reported adenosine-oligo-arginine conjugate-based (ARC-type) inhibitors, was solved. Structural elements important for interaction with the kinase were established with specifically modified derivatives of the lead compound. On the basis of this knowledge, a new generation of inhibitors, conjugates of adenosine-4'-dehydroxymethyl-4'-carboxylic acid moiety and oligo(D-arginine), was developed with inhibitory constants well into the subnanomolar range. The structural determinants of selectivity of the new compounds were established in assays with ROCK-II and PKBgamma.