5FL5

Three dimensional structure of human carbonic anhydrase IX in complex with 5-(1-(4-Methoxyphenyl)-1H-1,2,3-triazol-4-yl)thiophene-2- sulfonamide


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.05 Å
  • R-Value Free: 0.196 
  • R-Value Work: 0.158 
  • R-Value Observed: 0.160 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.5 of the entry. See complete history


Literature

An Efficient Expression and Crystallization System of the Cancer Asociated Carbonic Anhydrase Isoform Ix.

Leitans, J.Kazaks, A.Balode, A.Ivanova, J.Zalubovskis, R.Supuran, C.T.Tars, K.

(2015) J Med Chem 58: 9004

  • DOI: https://doi.org/10.1021/acs.jmedchem.5b01343
  • Primary Citation of Related Structures:  
    5FL4, 5FL5, 5FL6

  • PubMed Abstract: 

    Human carbonic anhydrase IX (CA IX) is overexpressed in a number of solid tumors and is considered to be a marker for cellular hypoxia that it is not produced in most normal tissues. CA IX contributes to the acidification of the extracellular matrix, which, in turn, favors tumor growth and metastasis. Therefore, CA IX is considered to be a promising anti-cancer drug target. However, the ability to specifically target CA IX is challenging due to the fact that the human genome encodes 15 different carbonic anhydrase isoforms that have a high degree of homology. Furthermore, structure-based drug design of CA IX inhibitors so far has been largely unsuccessful due to technical difficulties regarding the expression and crystallization of the enzyme. Currently, only one baculovirus-produced CA IX structure in complex with a nonspecific CA inhibitor, acetazolamide, is available in Protein Data Bank. We have developed an efficient system for the production of the catalytic domain of CA IX in methylotrophic yeast Pichia pastoris. The produced protein can be easily crystallized in the presence of inhibitors, as we have demonstrated for several 2-thiophene-sulfonamide compounds. We have also observed significant differences in the binding mode of chemically identical compounds to CA IX and CA II, which can be further exploited in the design of CA IX-specific inhibitors.


  • Organizational Affiliation

    Biomedical Research and Study Center , Ratsupites 1, LV-1067, Riga, Latvia.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
CARBONIC ANHYDRASE IX
A, B, C, D
257Homo sapiensMutation(s): 1 
EC: 4.2.1.1
UniProt & NIH Common Fund Data Resources
Find proteins for Q16790 (Homo sapiens)
Explore Q16790 
Go to UniProtKB:  Q16790
PHAROS:  Q16790
GTEx:  ENSG00000107159 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ16790
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 5 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
82E
Query on 82E

Download Ideal Coordinates CCD File 
E [auth A],
FA [auth D],
Q [auth B],
Z [auth C]
5-[1-(4-methoxyphenyl)-1,2,3-triazol-4-yl]thiophene-2-sulfonamide
C13 H12 N4 O3 S2
VMVUOOHEBHJELO-UHFFFAOYSA-N
TRS
Query on TRS

Download Ideal Coordinates CCD File 
LA [auth D],
P [auth A],
Y [auth B]
2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL
C4 H12 N O3
LENZDBCJOHFCAS-UHFFFAOYSA-O
SO4
Query on SO4

Download Ideal Coordinates CCD File 
CA [auth C]
DA [auth C]
EA [auth C]
H [auth A]
I [auth A]
CA [auth C],
DA [auth C],
EA [auth C],
H [auth A],
I [auth A],
IA [auth D],
J [auth A],
JA [auth D],
K [auth A],
KA [auth D],
L [auth A],
M [auth A],
N [auth A],
O [auth A],
T [auth B],
U [auth B],
V [auth B],
W [auth B],
X [auth B]
SULFATE ION
O4 S
QAOWNCQODCNURD-UHFFFAOYSA-L
GOL
Query on GOL

Download Ideal Coordinates CCD File 
BA [auth C],
G [auth A],
HA [auth D],
S [auth B]
GLYCEROL
C3 H8 O3
PEDCQBHIVMGVHV-UHFFFAOYSA-N
ZN
Query on ZN

Download Ideal Coordinates CCD File 
AA [auth C],
F [auth A],
GA [auth D],
R [auth B]
ZINC ION
Zn
PTFCDOFLOPIGGS-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
82E Binding MOAD:  5FL5 Ki: 6.4 (nM) from 1 assay(s)
BindingDB:  5FL5 Ki: 6.4 (nM) from 1 assay(s)
SO4 BindingDB:  5FL5 Ki: 1.54e+8 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.05 Å
  • R-Value Free: 0.196 
  • R-Value Work: 0.158 
  • R-Value Observed: 0.160 
  • Space Group: H 3
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 152.38α = 90
b = 152.38β = 90
c = 170.59γ = 120
Software Package:
Software NamePurpose
REFMACrefinement
MOSFLMdata reduction
SCALAdata scaling
MOLREPphasing

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2015-11-11
    Type: Initial release
  • Version 1.1: 2015-12-09
    Changes: Database references
  • Version 1.2: 2018-01-17
    Changes: Data collection
  • Version 1.3: 2019-01-30
    Changes: Data collection, Experimental preparation
  • Version 1.4: 2019-02-06
    Changes: Data collection, Experimental preparation
  • Version 1.5: 2024-01-10
    Changes: Data collection, Database references, Derived calculations, Other, Refinement description