3BL1

Carbonic anhydrase inhibitors. Sulfonamide diuretics revisited old leads for new applications


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.10 Å
  • R-Value Free: 0.299 
  • R-Value Work: 0.224 
  • R-Value Observed: 0.228 

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Ligand Structure Quality Assessment 


This is version 1.4 of the entry. See complete history


Literature

Carbonic anhydrase inhibitors. Interaction of indapamide and related diuretics with 12 mammalian isozymes and X-ray crystallographic studies for the indapamide-isozyme II adduct.

Temperini, C.Cecchi, A.Scozzafava, A.Supuran, C.T.

(2008) Bioorg Med Chem Lett 18: 2567-2573

  • DOI: https://doi.org/10.1016/j.bmcl.2008.03.051
  • Primary Citation of Related Structures:  
    3BL1

  • PubMed Abstract: 

    Diuretics such as hydrochlorothiazide, hydroflumethiazide, quinethazone, metolazone, chlorthalidone, indapamide, furosemide, and bumetanide containing primary sulfamoyl moieties were reevaluated as inhibitors of 12 human carbonic anhydrases (hCAs, EC 4.2.1.1). These drugs considerably inhibit (low nanomolar range) some CA isozymes involved in critical physiologic processes, among the 16 present in vertebrates, for example, metolazone against CA VII, XII, and XIII, chlorthalidone against CA VB, VII, IX, XII, and XIII, indapamide against CA VII, IX, XII, and XIII, furosemide against CA I, II, and XIV, and bumetanide against CA IX and XII. The X-ray crystal structure of the hCA II-indapamide adduct was also resolved at high resolution.


  • Organizational Affiliation

    Università degli Studi di Firenze, Laboratorio di Chimica Bioinorganica, Room 188, Via della Lastruccia 3, I-50019 Sesto Fiorentino (Firenze), Italy.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Carbonic anhydrase 2260Homo sapiensMutation(s): 0 
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
BL1
Query on BL1

Download Ideal Coordinates CCD File 
D [auth A]4-chloro-N-[(2S)-2-methyl-2,3-dihydro-1H-indol-1-yl]-3-sulfamoylbenzamide
C16 H16 Cl N3 O3 S
NDDAHWYSQHTHNT-JTQLQIEISA-N
HG
Query on HG

Download Ideal Coordinates CCD File 
C [auth A]MERCURY (II) ION
Hg
BQPIGGFYSBELGY-UHFFFAOYSA-N
ZN
Query on ZN

Download Ideal Coordinates CCD File 
B [auth A]ZINC ION
Zn
PTFCDOFLOPIGGS-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
BL1 Binding MOAD:  3BL1 Ki: 2520 (nM) from 1 assay(s)
PDBBind:  3BL1 Ki: 2520 (nM) from 1 assay(s)
BindingDB:  3BL1 Ki: min: 2520, max: 2.52e+6 (nM) from 2 assay(s)
Kd: min: 3.8, max: 530 (nM) from 4 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.10 Å
  • R-Value Free: 0.299 
  • R-Value Work: 0.224 
  • R-Value Observed: 0.228 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 42.05α = 90
b = 41.32β = 104.29
c = 72.25γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
CrysalisProdata collection
CrysalisProdata reduction
SCALAdata scaling
AMoREphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2008-07-01
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2017-10-25
    Changes: Refinement description
  • Version 1.3: 2018-04-04
    Changes: Data collection, Source and taxonomy
  • Version 1.4: 2024-02-21
    Changes: Data collection, Database references, Derived calculations