PDBsum entry 6ynb

Transferase

PDB id: 6ynb

Contents

Protein chains

349 a.a.

13 a.a.

Ligands

IQU

DMS

Waters ×254

PDB id:

6ynb

Name:

Transferase

Title:

Crystal structure of camp-dependent protein kinase (pka) in complex with short-chain fasudil-derivative n-(2-aminoethyl)isoquinoline-5- sulfonamide (soaked)

Structure:

Camp-dependent protein kinase catalytic subunit alpha. Chain: a. Synonym: pka c-alpha. Engineered: yes. Camp-dependent protein kinase inhibitor alpha. Chain: b. Synonym: pki-alpha,camp-dependent protein kinase inhibitor, muscle/brain isoform. Engineered: yes

Source:

Cricetulus griseus. Chinese hamster. Organism_taxid: 10029. Gene: prkaca. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008. Synthetic: yes. Mus musculus. House mouse.

Resolution:

1.72Å R-factor: 0.158 R-free: 0.201

Authors:

M.Oebbeke,B.Wienen-Schmidt,A.Heine,G.Klebe

Key ref:

B.Wienen-Schmidt et al. (2021). Two Methods, One Goal: Structural Differences between Cocrystallization and Crystal Soaking to Discover Ligand Binding Poses. ChemMedChem, 16, 292-300. PubMed id: 33029876 DOI: 10.1002/cmdc.202000565

Date:

13-Apr-20 Release date: 14-Oct-20

Protein chain

P25321  (KAPCA_CRIGR) -  cAMP-dependent protein kinase catalytic subunit alpha from Cricetulus griseus

Seq: 351 a.a.

Struc: 349 a.a.*

Protein chain

P63248  (IPKA_MOUSE) -  cAMP-dependent protein kinase inhibitor alpha from Mus musculus

Seq: 76 a.a.

Struc: 13 a.a.*

* PDB and UniProt seqs differ at 3 residue positions (black crosses)

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: 10.1002/cmdc.202000565

ChemMedChem 16:292-300 (2021)

PubMed id: 33029876

Two Methods, One Goal: Structural Differences between Cocrystallization and Crystal Soaking to Discover Ligand Binding Poses.

B.Wienen-Schmidt, M.Oebbeke, K.Ngo, A.Heine, G.Klebe.

ABSTRACT

In lead optimization, protein crystallography is an indispensable tool to analyze drug binding. Binding modes and non-covalent interaction inventories are essential to design follow-up synthesis candidates. Two protocols are commonly applied to produce protein-ligand complexes: cocrystallization and soaking. Because of its time and cost effectiveness, soaking is the more popular method. Taking eight ligand hinge binders of protein kinase A, we demonstrate that cocrystallization is superior. Particularly for flexible proteins, such as kinases, and larger ligands cocrystallization captures more reliable the correct binding pose and induced protein adaptations. The geometrical discrepancies between soaking and cocrystallization appear smaller for fragment-sized ligands. For larger flexible ligands that trigger conformational changes of the protein, soaking can be misleading and underestimates the number of possible polar interactions due to inadequate, highly impaired positions of protein amino-acid side and main chain atoms. Thus, if applicable cocrystallization should be the gold standard to study protein-ligand complexes.