5I2R

human PDE10A in complex with 3-(2-phenylpyrazol-3-yl)-1-[3-(trifluoromethoxy)phenyl]pyridazin-4-one


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.50 Å
  • R-Value Free: 0.250 
  • R-Value Work: 0.191 
  • R-Value Observed: 0.194 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.0 of the entry. See complete history


Literature

A Real-World Perspective on Molecular Design.

Kuhn, B.Guba, W.Hert, J.Banner, D.Bissantz, C.Ceccarelli, S.Haap, W.Korner, M.Kuglstatter, A.Lerner, C.Mattei, P.Neidhart, W.Pinard, E.Rudolph, M.G.Schulz-Gasch, T.Woltering, T.Stahl, M.

(2016) J Med Chem 59: 4087-4102

  • DOI: https://doi.org/10.1021/acs.jmedchem.5b01875
  • Primary Citation of Related Structures:  
    5EDB, 5EDC, 5EDE, 5EDG, 5EDH, 5EDI, 5EZX, 5EZZ, 5F00, 5F01, 5F02, 5F03, 5I2R

  • PubMed Abstract: 

    We present a series of small molecule drug discovery case studies where computational methods were prospectively employed to impact Roche research projects, with the aim of highlighting those methods that provide real added value. Our brief accounts encompass a broad range of methods and techniques applied to a variety of enzymes and receptors. Most of these are based on judicious application of knowledge about molecular conformations and interactions: filling of lipophilic pockets to gain affinity or selectivity, addition of polar substituents, scaffold hopping, transfer of SAR, conformation analysis, and molecular overlays. A case study of sequence-driven focused screening is presented to illustrate how appropriate preprocessing of information enables effective exploitation of prior knowledge. We conclude that qualitative statements enabling chemists to focus on promising regions of chemical space are often more impactful than quantitative prediction.


  • Organizational Affiliation

    Roche Pharmaceutical Research and Early Development, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd. , Grenzacherstrasse 124, 4070 Basel, Switzerland.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A
A, B, C, D
318Homo sapiensMutation(s): 0 
Gene Names: PDE10A
EC: 3.1.4.17 (PDB Primary Data), 3.1.4.35 (PDB Primary Data)
UniProt & NIH Common Fund Data Resources
Find proteins for Q9Y233 (Homo sapiens)
Explore Q9Y233 
Go to UniProtKB:  Q9Y233
PHAROS:  Q9Y233
GTEx:  ENSG00000112541 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ9Y233
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 3 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
67A
Query on 67A

Download Ideal Coordinates CCD File 
G [auth A],
J [auth B],
M [auth C],
P [auth D]
3-(1-phenyl-1H-pyrazol-5-yl)-1-[3-(trifluoromethoxy)phenyl]pyridazin-4(1H)-one
C20 H13 F3 N4 O2
NAIXHNHQENAMNS-UHFFFAOYSA-N
ZN
Query on ZN

Download Ideal Coordinates CCD File 
E [auth A],
H [auth B],
K [auth C],
N [auth D]
ZINC ION
Zn
PTFCDOFLOPIGGS-UHFFFAOYSA-N
MG
Query on MG

Download Ideal Coordinates CCD File 
F [auth A],
I [auth B],
L [auth C],
O [auth D]
MAGNESIUM ION
Mg
JLVVSXFLKOJNIY-UHFFFAOYSA-N
Modified Residues  1 Unique
IDChains TypeFormula2D DiagramParent
CME
Query on CME
A, B, C, D
L-PEPTIDE LINKINGC5 H11 N O3 S2CYS
Binding Affinity Annotations 
IDSourceBinding Affinity
67A Binding MOAD:  5I2R IC50: 19 (nM) from 1 assay(s)
BindingDB:  5I2R IC50: 14 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.50 Å
  • R-Value Free: 0.250 
  • R-Value Work: 0.191 
  • R-Value Observed: 0.194 
  • Space Group: H 3
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 135.809α = 90
b = 135.809β = 90
c = 234.864γ = 120
Software Package:
Software NamePurpose
REFMACrefinement
XSCALEdata scaling
PDB_EXTRACTdata extraction
XDSdata reduction
REFMACphasing

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2016-03-09
    Type: Initial release