PDBsum entry 4ij9

Transferase/transferase inhibitor

PDB id: 4ij9

Contents

Protein chains

337 a.a.

18 a.a.

Ligands

PTV

Waters ×234

PDB id:

4ij9

Name:

Transferase/transferase inhibitor

Title:

Bovine pka c-alpha in complex with 2-[[5-(4-pyridyl)-1h-1,2,4-triazol- 3-yl]sulfanyl]-1-(2-thiophenyl)ethanone

Structure:

Camp-dependent protein kinase catalytic subunit alpha. Chain: a. Synonym: pka c-alpha. Engineered: yes. Camp-dependent protein kinase inhibitor alpha. Chain: i. Fragment: unp residues 6-25. Synonym: pki-alpha, camp-dependent protein kinase inhibitor, muscle/brain isoform.

Source:

Bos taurus. Bovine. Organism_taxid: 9913. Gene: prkaca. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes. Homo sapiens. Human.

Resolution:

2.55Å R-factor: 0.175 R-free: 0.248

Authors:

M.K.Dreyer,A.Schiffer

Key ref:

L.Skjærven et al. (2013). Accounting for conformational variability in protein-ligand docking with NMR-guided rescoring. J Am Chem Soc, 135, 5819-5827. PubMed id: 23565800 DOI: 10.1021/ja4007468

Date:

21-Dec-12 Release date: 01-May-13

Protein chain

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

Seq: 351 a.a.

Struc: 337 a.a.*

Protein chain

P61925  (IPKA_HUMAN) -  cAMP-dependent protein kinase inhibitor alpha from Homo sapiens

Seq: 76 a.a.

Struc: 18 a.a.

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

Enzyme reactions

• Enzyme class: Chain A: 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

DOI no: 10.1021/ja4007468

J Am Chem Soc 135:5819-5827 (2013)

PubMed id: 23565800

Accounting for conformational variability in protein-ligand docking with NMR-guided rescoring.

L.Skjærven, L.Codutti, A.Angelini, M.Grimaldi, D.Latek, P.Monecke, M.K.Dreyer, T.Carlomagno.

ABSTRACT

A key component to success in structure-based drug design is reliable information on protein-ligand interactions. Recent development in NMR techniques has accelerated this process by overcoming some of the limitations of X-ray crystallography and computational protein-ligand docking. In this work we present a new scoring protocol based on NMR-derived interligand INPHARMA NOEs to guide the selection of computationally generated docking modes. We demonstrate the performance in a range of scenarios, encompassing traditionally difficult cases such as docking to homology models and ligand dependent domain rearrangements. Ambiguities associated with sparse experimental information are lifted by searching a consensus solution based on simultaneously fitting multiple ligand pairs. This study provides a previously unexplored integration between molecular modeling and experimental data, in which interligand NOEs represent the key element in the rescoring algorithm. The presented protocol should be widely applicable for protein-ligand docking also in a different context from drug design and highlights the important role of NMR-based approaches to describe intermolecular ligand-receptor interactions.