5TV3

Crystal structure of the complex of Helicobacter pylori alpha-carbonic anhydrase with (E)-5-(((4-(tert-butyl)phenyl)sulfonyl)imino)-4-methyl-4,5-dihydro-1,3,4-thiadiazole-2-sulfonamide


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.90 Å
  • R-Value Free: 0.243 
  • R-Value Work: 0.187 
  • R-Value Observed: 0.192 

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Ligand Structure Quality Assessment 


This is version 1.1 of the entry. See complete history


Literature

Structure-Activity Relationship for Sulfonamide Inhibition of Helicobacter pylori alpha-Carbonic Anhydrase.

Modak, J.K.Liu, Y.C.Supuran, C.T.Roujeinikova, A.

(2016) J Med Chem 59: 11098-11109

  • DOI: https://doi.org/10.1021/acs.jmedchem.6b01333
  • Primary Citation of Related Structures:  
    5TT3, 5TT8, 5TUO, 5TV3

  • PubMed Abstract: 

    α-Carbonic anhydrase of Helicobacter pylori (HpαCA) plays an important role in the acclimation of this oncobacterium to the acidic pH of the stomach. Sulfonamide inhibitors of HpαCA possess anti-H. pylori activity. The crystal structures of complexes of HpαCA with a family of acetazolamide-related sulfonamides have been determined. Analysis of the structures revealed that the mode of sulfonamide binding correlates well with their inhibitory activities. In addition, comparisons with the corresponding inhibitor complexes of human carbonic anhydrase II (HCAII) indicated that HpαCA possesses an additional, alternative binding site for sulfonamides that is not present in HCAII. Furthermore, the hydrophobic pocket in HCAII that stabilizes the apolar moiety of sulfonamide inhibitors is replaced with a more open, hydrophilic pocket in HpαCA. Thus, our analysis identified major structural features can be exploited in the design of selective and more potent inhibitors of HpαCA that may lead to novel antimicrobials.


  • Organizational Affiliation

    Department of Microbiology, Monash University , Clayton, Victoria 3800, Australia.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Alpha-carbonic anhydrase
A, B, C, D, E
A, B, C, D, E, F, G, H
234Helicobacter pylori 26695Mutation(s): 0 
Gene Names: C694_06140
EC: 4.2.1.1
UniProt
Find proteins for A0A0M3KL20 (Helicobacter pylori (strain ATCC 700392 / 26695))
Explore A0A0M3KL20 
Go to UniProtKB:  A0A0M3KL20
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupA0A0M3KL20
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 4 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
7L3
Query on 7L3

Download Ideal Coordinates CCD File 
AA [auth H]
J [auth A]
L [auth B]
O [auth C]
R [auth D]
AA [auth H],
J [auth A],
L [auth B],
O [auth C],
R [auth D],
T [auth E],
V [auth F],
Y [auth G]
(5Z)-5-{[(4-tert-butylphenyl)sulfonyl]imino}-4-methyl-4,5-dihydro-1,3,4-thiadiazole-2-sulfonamide
C13 H18 N4 O4 S3
NSQKDLKNBCRMRT-WJDWOHSUSA-N
GOL
Query on GOL

Download Ideal Coordinates CCD File 
N [auth C]GLYCEROL
C3 H8 O3
PEDCQBHIVMGVHV-UHFFFAOYSA-N
ZN
Query on ZN

Download Ideal Coordinates CCD File 
I [auth A]
K [auth B]
M [auth C]
P [auth D]
S [auth E]
I [auth A],
K [auth B],
M [auth C],
P [auth D],
S [auth E],
U [auth F],
W [auth G],
Z [auth H]
ZINC ION
Zn
PTFCDOFLOPIGGS-UHFFFAOYSA-N
CL
Query on CL

Download Ideal Coordinates CCD File 
Q [auth D],
X [auth G]
CHLORIDE ION
Cl
VEXZGXHMUGYJMC-UHFFFAOYSA-M
Binding Affinity Annotations 
IDSourceBinding Affinity
CL BindingDB:  5TV3 Ki: 2.70e+6 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.90 Å
  • R-Value Free: 0.243 
  • R-Value Work: 0.187 
  • R-Value Observed: 0.192 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 41.56α = 90
b = 133.89β = 90.3
c = 166.6γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
SCALAdata scaling
PDB_EXTRACTdata extraction
iMOSFLMdata reduction
PHENIXphasing
ADSCdata collection

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2017-09-20
    Type: Initial release
  • Version 1.1: 2023-10-04
    Changes: Data collection, Database references, Derived calculations, Refinement description