4IE9

Bovine PKA C-alpha in complex with 3-pyridylmethyl-5-methyl-1H-pyrazole-3-carboxylate


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.92 Å
  • R-Value Free: 0.232 
  • R-Value Work: 0.177 
  • R-Value Observed: 0.180 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.1 of the entry. See complete history


Literature

Accounting for Conformational Variability in Protein-Ligand Docking with NMR-Guided Rescoring

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

(2013) J Am Chem Soc 135: 5819-5827

  • DOI: https://doi.org/10.1021/ja4007468
  • Primary Citation of Related Structures:  
    4IE9, 4IJ9

  • PubMed 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.


  • Organizational Affiliation

    EMBL, Structural and Computational Biology Unit, Meyerhofstrasse 1, D-69117 Heidelberg, Germany.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
cAMP-dependent protein kinase catalytic subunit alpha351Bos taurusMutation(s): 0 
Gene Names: PRKACA
EC: 2.7.11.11
UniProt
Find proteins for P00517 (Bos taurus)
Explore P00517 
Go to UniProtKB:  P00517
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP00517
Sequence Annotations
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  • Reference Sequence

Find similar proteins by:  Sequence   |   3D Structure  

Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
cAMP-dependent protein kinase inhibitor alphaB [auth I]20Homo sapiensMutation(s): 0 
UniProt & NIH Common Fund Data Resources
Find proteins for P61925 (Homo sapiens)
Explore P61925 
Go to UniProtKB:  P61925
PHAROS:  P61925
GTEx:  ENSG00000171033 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP61925
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
PZX
Query on PZX

Download Ideal Coordinates CCD File 
C [auth A]pyridin-3-ylmethyl 5-methyl-1H-pyrazole-3-carboxylate
C11 H11 N3 O2
VPQUTEUTVVBFOS-UHFFFAOYSA-N
GOL
Query on GOL

Download Ideal Coordinates CCD File 
D [auth A]GLYCEROL
C3 H8 O3
PEDCQBHIVMGVHV-UHFFFAOYSA-N
Modified Residues  2 Unique
IDChains TypeFormula2D DiagramParent
SEP
Query on SEP
A
L-PEPTIDE LINKINGC3 H8 N O6 PSER
TPO
Query on TPO
A
L-PEPTIDE LINKINGC4 H10 N O6 PTHR
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.92 Å
  • R-Value Free: 0.232 
  • R-Value Work: 0.177 
  • R-Value Observed: 0.180 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 73.06α = 90
b = 75.32β = 90
c = 79.88γ = 90
Software Package:
Software NamePurpose
MAR345data collection
AMoREphasing
BUSTERrefinement
XDSdata reduction
SCALAdata scaling

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2013-05-01
    Type: Initial release
  • Version 1.1: 2017-11-15
    Changes: Refinement description