5NY6

Carbonic Anhydrase II Inhibitor RA12


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.10 Å
  • R-Value Free: 0.154 
  • R-Value Work: 0.139 
  • R-Value Observed: 0.139 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.3 of the entry. See complete history


Literature

Ranking Power of the SQM/COSMO Scoring Function on Carbonic Anhydrase II-Inhibitor Complexes.

Pecina, A.Brynda, J.Vrzal, L.Gnanasekaran, R.Horejsi, M.Eyrilmez, S.M.Rezac, J.Lepsik, M.Rezacova, P.Hobza, P.Majer, P.Veverka, V.Fanfrlik, J.

(2018) Chemphyschem 19: 873-879

  • DOI: https://doi.org/10.1002/cphc.201701104
  • Primary Citation of Related Structures:  
    5NXG, 5NXI, 5NXM, 5NXO, 5NXP, 5NXV, 5NXW, 5NY1, 5NY3, 5NY6, 5NYA

  • PubMed Abstract: 

    Accurate prediction of protein-ligand binding affinities is essential for hit-to-lead optimization and virtual screening. The reliability of scoring functions can be improved by including quantum effects. Here, we demonstrate the ranking power of the semiempirical quantum mechanics (SQM)/implicit solvent (COSMO) scoring function by using a challenging set of 10 inhibitors binding to carbonic anhydrase II through Zn 2+ in the active site. This new dataset consists of the high-resolution (1.1-1.4 Å) crystal structures and experimentally determined inhibitory constant (K i ) values. It allows for evaluation of the common approximations, such as representing the solvent implicitly or by using a single target conformation combined with a set of ligand docking poses. SQM/COSMO attained a good correlation of R 2 of 0.56-0.77 with the experimental inhibitory activities, benefiting from careful handling of both noncovalent interactions (e.g. charge transfer) and solvation. This proof-of-concept study of SQM/COSMO ranking for metalloprotein-ligand systems demonstrates its potential for hit-to-lead applications.


  • Organizational Affiliation

    Institute of Organic Chemistry and Biochemistry of the, Czech Academy of Sciences, Flemingovo nam. 2, 16610, Prague 6, Czech Republic.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Carbonic anhydrase 2258Homo sapiensMutation(s): 0 
Gene Names: CA2
EC: 4.2.1.1
UniProt & NIH Common Fund Data Resources
Find proteins for P00918 (Homo sapiens)
Explore P00918 
Go to UniProtKB:  P00918
PHAROS:  P00918
GTEx:  ENSG00000104267 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP00918
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 3 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
R92
Query on R92

Download Ideal Coordinates CCD File 
D [auth A]4-chloranyl-~{N}-[(1~{S})-1-(2-hydroxyphenyl)ethyl]-3-sulfamoyl-benzamide
C15 H15 Cl N2 O4 S
YTZRBQIEUYQFPK-VIFPVBQESA-N
9EB
Query on 9EB

Download Ideal Coordinates CCD File 
C [auth A]4-chloranyl-~{N}-[(1~{R})-1-(2-hydroxyphenyl)ethyl]-3-sulfamoyl-benzamide
C15 H15 Cl N2 O4 S
YTZRBQIEUYQFPK-SECBINFHSA-N
ZN
Query on ZN

Download Ideal Coordinates CCD File 
B [auth A]ZINC ION
Zn
PTFCDOFLOPIGGS-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
R92 Binding MOAD:  5NY6 Ki: 13.5 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.10 Å
  • R-Value Free: 0.154 
  • R-Value Work: 0.139 
  • R-Value Observed: 0.139 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 42.013α = 90
b = 41.107β = 104.23
c = 72.077γ = 90
Software Package:
Software NamePurpose
XSCALEdata scaling
REFMACrefinement
PDB_EXTRACTdata extraction
XDSdata reduction

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
Czech Science FoundationCzech RepublicGA15-05677S
IMG of the Czech Academy of SciencesCzech RepublicRVO 61388963
IOCB of the Czech Academy of SciencesCzech RepublicRVO 68378050
Ministry of EducationCzech RepublicLO1304

Revision History  (Full details and data files)

  • Version 1.0: 2018-01-17
    Type: Initial release
  • Version 1.1: 2018-01-24
    Changes: Experimental preparation
  • Version 1.2: 2018-04-18
    Changes: Data collection, Database references
  • Version 1.3: 2024-01-17
    Changes: Advisory, Data collection, Database references, Derived calculations, Refinement description