5LLP

Crystal structure of human carbonic anhydrase isozyme XII with 3-[(1S)-1,2,3,4-Tetrahydronapthalen-1-ylamino)-2,5,6-trifluoro-4-[(2-hydroxyethyl)sulfonyl]benzenesulfonamide


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.48 Å
  • R-Value Free: 0.199 
  • R-Value Work: 0.164 
  • R-Value Observed: 0.167 

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This is version 1.4 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 12
A, B, C, D
263Homo sapiensMutation(s): 0 
Gene Names: CA12
EC: 4.2.1.1
UniProt & NIH Common Fund Data Resources
Find proteins for O43570 (Homo sapiens)
Explore O43570 
Go to UniProtKB:  O43570
PHAROS:  O43570
GTEx:  ENSG00000074410 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupO43570
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.48 Å
  • R-Value Free: 0.199 
  • R-Value Work: 0.164 
  • R-Value Observed: 0.167 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 77.488α = 90
b = 74.288β = 108.97
c = 91.658γ = 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: 2017-11-22
    Changes: Database references, Structure summary
  • Version 1.2: 2017-11-29
    Changes: Database references
  • Version 1.3: 2018-05-16
    Changes: Data collection, Database references
  • Version 1.4: 2024-01-10
    Changes: Data collection, Database references, Derived calculations, Refinement description