5DVX

Crystal structure of the catalytic-domain of human carbonic anhydrase IX at 1.6 angstrom resolution


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.60 Å
  • R-Value Free: 0.191 
  • R-Value Work: 0.168 
  • R-Value Observed: 0.168 

wwPDB Validation   3D Report Full Report


This is version 1.5 of the entry. See complete history


Literature

The Structure of Carbonic Anhydrase IX Is Adapted for Low-pH Catalysis.

Mahon, B.P.Bhatt, A.Socorro, L.Driscoll, J.M.Okoh, C.Lomelino, C.L.Mboge, M.Y.Kurian, J.J.Tu, C.Agbandje-McKenna, M.Frost, S.C.McKenna, R.

(2016) Biochemistry 55: 4642-4653

  • DOI: https://doi.org/10.1021/acs.biochem.6b00243
  • Primary Citation of Related Structures:  
    5DVX

  • PubMed Abstract: 

    Human carbonic anhydrase IX (hCA IX) expression in many cancers is associated with hypoxic tumors and poor patient outcome. Inhibitors of hCA IX have been used as anticancer agents with some entering Phase I clinical trials. hCA IX is transmembrane protein whose catalytic domain faces the extracellular tumor milieu, which is typically associated with an acidic microenvironment. Here, we show that the catalytic domain of hCA IX (hCA IX-c) exhibits the necessary biochemical and biophysical properties that allow for low pH stability and activity. Furthermore, the unfolding process of hCA IX-c appears to be reversible, and its catalytic efficiency is thought to be correlated directly with its stability between pH 3.0 and 8.0 but not above pH 8.0. To rationalize this, we determined the X-ray crystal structure of hCA IX-c to 1.6 Å resolution. Insights from this study suggest an understanding of hCA IX-c stability and activity in low-pH tumor microenvironments and may be applicable to determining pH-related effects on enzymes.


  • Organizational Affiliation

    Department of Biochemistry and Molecular Biology, University of Florida College of Medicine , Gainesville, Florida 32610, United States.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Carbonic anhydrase 9
A, B
260Homo sapiensMutation(s): 6 
Gene Names: CA9G250MN
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 4 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
TRS
Query on TRS

Download Ideal Coordinates CCD File 
J [auth A]2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL
C4 H12 N O3
LENZDBCJOHFCAS-UHFFFAOYSA-O
GOL
Query on GOL

Download Ideal Coordinates CCD File 
E [auth A]
F [auth A]
G [auth A]
M [auth B]
N [auth B]
E [auth A],
F [auth A],
G [auth A],
M [auth B],
N [auth B],
O [auth B]
GLYCEROL
C3 H8 O3
PEDCQBHIVMGVHV-UHFFFAOYSA-N
ZN
Query on ZN

Download Ideal Coordinates CCD File 
C [auth A],
D [auth A],
K [auth A],
L [auth B]
ZINC ION
Zn
PTFCDOFLOPIGGS-UHFFFAOYSA-N
CL
Query on CL

Download Ideal Coordinates CCD File 
H [auth A],
I [auth A],
P [auth B]
CHLORIDE ION
Cl
VEXZGXHMUGYJMC-UHFFFAOYSA-M
Binding Affinity Annotations 
IDSourceBinding Affinity
CL BindingDB:  5DVX Ki: 3.30e+7 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.60 Å
  • R-Value Free: 0.191 
  • R-Value Work: 0.168 
  • R-Value Observed: 0.168 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 57.877α = 90
b = 102.744β = 90
c = 108.964γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
HKL-2000data collection
HKL-2000data scaling
PDB_EXTRACTdata extraction
HKL-2000data reduction
PHENIXphasing

Structure Validation

View Full Validation Report



Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
National Institutes of Health/National Cancer Institute (NIH/NCI)United StatesCA165284

Revision History  (Full details and data files)

  • Version 1.0: 2016-08-03
    Type: Initial release
  • Version 1.1: 2016-08-17
    Changes: Database references
  • Version 1.2: 2016-09-07
    Changes: Database references
  • Version 1.3: 2017-09-27
    Changes: Author supporting evidence, Database references, Derived calculations
  • Version 1.4: 2019-12-04
    Changes: Author supporting evidence
  • Version 1.5: 2023-09-27
    Changes: Advisory, Data collection, Database references, Derived calculations, Refinement description