1ZE8: Carbonic Anhydrase Ii In Complex With A Membrane-Impermeant Sulfonamide Inhibitor

Citation:
Abstract
Structure for the adduct of carbonic anhydrase II with 1-N-(4-sulfamoylphenyl-ethyl)-2,4,6-trimethylpyridinium perchlorate, a membrane-impermeant antitumor sulfonamide, is reported. The phenylethyl moiety fills the active site, making van der Waals interactions with side chains of Gln192, Val121, Phe131, Leu198, Thr200. The 2,4,6-trimethylpyridinium functionality is at van der Waals distance from the aliphatic chain of Ile91 being involved in strong offset face-to-face stacking with Phe131. Analyzing X-ray crystal structures of such adducts, two binding modes were observed: some inhibitors bind with their tail within the hydrophobic half of the active site, defined by residues Phe131, Val135, Leu198, Pro202, Leu204. Other derivatives bind with their tail in a different region, pointing toward the hydrophilic half and making strong parallel stacking with Phe131. This interaction orients the inhibitor toward the hydrophilic part of the active site. Impossibility to participate in it leads to its binding within the hydrophobic half. Such findings are relevant for designing better inhibitors targeting isozymes II, IX, and XII, some of which are overexpressed in hypoxic tumors.
PDB ID: 1ZE8Download
MMDB ID: 35545
PDB Deposition Date: 2005/4/18
Updated in MMDB: 2012/11
Experimental Method:
x-ray diffraction
Resolution: 2  Å
Source Organism:
Similar Structures:
Biological Unit for 1ZE8: monomeric; determined by author
Molecular Components in 1ZE8
Label Count Molecule
Protein (1 molecule)
1
Carbonic Anhydrase II(Gene symbol: CA2)
Molecule annotation
Chemicals (4 molecules)
1
1
2
1
3
1
4
1
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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