5LLC

Crystal structure of human carbonic anhydrase isozyme II with 3-(Methylamino)-2,5,6-trifluoro-4-[(2-phenylethyl)sulfonyl]benzenesulfonamide


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.10 Å
  • R-Value Free: 0.161 
  • R-Value Work: 0.138 
  • R-Value Observed: 0.140 

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Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history


Literature

Crystal structure correlations with the intrinsic thermodynamics of human carbonic anhydrase inhibitor binding.

Smirnov, A.Zubriene, A.Manakova, E.Grazulis, S.Matulis, D.

(2018) PeerJ 6: e4412-e4412

  • DOI: https://doi.org/10.7717/peerj.4412
  • Primary Citation of Related Structures:  
    5LLC, 5LLE, 5LLG, 5LLH, 5LLO, 5LLP, 5MSB

  • PubMed Abstract: 

    The structure-thermodynamics correlation analysis was performed for a series of fluorine- and chlorine-substituted benzenesulfonamide inhibitors binding to several human carbonic anhydrase (CA) isoforms. The total of 24 crystal structures of 16 inhibitors bound to isoforms CA I, CA II, CA XII, and CA XIII provided the structural information of selective recognition between a compound and CA isoform. The binding thermodynamics of all structures was determined by the analysis of binding-linked protonation events, yielding the intrinsic parameters, i.e., the enthalpy, entropy, and Gibbs energy of binding. Inhibitor binding was compared within structurally similar pairs that differ by para- or meta -substituents enabling to obtain the contributing energies of ligand fragments. The pairs were divided into two groups. First, similar binders-the pairs that keep the same orientation of the benzene ring exhibited classical hydrophobic effect, a less exothermic enthalpy and a more favorable entropy upon addition of the hydrophobic fragments. Second, dissimilar binders-the pairs of binders that demonstrated altered positions of the benzene rings exhibited the non-classical hydrophobic effect, a more favorable enthalpy and variable entropy contribution. A deeper understanding of the energies contributing to the protein-ligand recognition should lead toward the eventual goal of rational drug design where chemical structures of ligands could be designed based on the target protein structure.


  • Organizational Affiliation

    Department of Biothermodynamics and Drug Design, Institute of Biotechnology, Vilnius University, Vilnius, Lithuania.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Carbonic anhydrase 2260Homo 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 4 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
V26
Query on V26

Download Ideal Coordinates CCD File 
I [auth A]2,3,6-tris(fluoranyl)-5-(methylamino)-4-(2-phenylethylsulfonyl)benzenesulfonamide
C15 H15 F3 N2 O4 S2
WQFYXDRMKJAGFX-UHFFFAOYSA-N
DMS
Query on DMS

Download Ideal Coordinates CCD File 
C [auth A],
D [auth A]
DIMETHYL SULFOXIDE
C2 H6 O S
IAZDPXIOMUYVGZ-UHFFFAOYSA-N
ZN
Query on ZN

Download Ideal Coordinates CCD File 
B [auth A]ZINC ION
Zn
PTFCDOFLOPIGGS-UHFFFAOYSA-N
EDO
Query on EDO

Download Ideal Coordinates CCD File 
E [auth A],
F [auth A],
G [auth A],
H [auth A]
1,2-ETHANEDIOL
C2 H6 O2
LYCAIKOWRPUZTN-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
V26 BindingDB:  5LLC Kd: min: 2.4, max: 8.2 (nM) from 4 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.10 Å
  • R-Value Free: 0.161 
  • R-Value Work: 0.138 
  • R-Value Observed: 0.140 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 42.209α = 90
b = 41.078β = 104.11
c = 71.968γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
SCALAdata scaling
PDB_EXTRACTdata extraction
XDSdata reduction
MOLREPphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2017-08-16
    Type: Initial release
  • Version 1.1: 2018-05-16
    Changes: Data collection, Database references
  • Version 1.2: 2024-01-10
    Changes: Data collection, Database references, Refinement description