4RN4: Human Carbonic Anhydrases Ii In Complex With A Acetazolamide Derivative Comprising One Hydrophobic And One Hydrophilic Tail Moiety

We present a new approach to carbonic anhydrase II (CA II) inhibitor design that enables close interrogation of the regions of the CA active site where there is the greatest variability in amino acid residues among the different CA isozymes. By appending dual tail groups onto the par excellence CA inhibitor acetazolamide, compounds that may interact with the distinct hydrophobic and hydrophilic halves of the CA II active site were prepared. The dual-tail combinations selected included (i) two hydrophobic moieties, (ii) two hydrophilic moieties, and (iii) one hydrophobic and one hydrophilic moiety. The CA enzyme inhibition profile as well as the protein X-ray crystal structure of compound 3, comprising one hydrophobic and one hydrophilic tail moiety, in complex with CA II is described. This novel dual-tail approach has provided an enhanced opportunity to more fully exploit interactions with the CA active site by enabling these molecules to interact with the distinct halves of the active site. In addition to the dual-tail compounds, a corresponding set of single-tail derivatives was synthesized, enabling a comparative analysis of the single-tail versus dual-tail compound CA inhibition profile.
PDB ID: 4RN4Download
MMDB ID: 126474
PDB Deposition Date: 2014/10/22
Updated in MMDB: 2015/02
Experimental Method:
x-ray diffraction
Resolution: 1.53  Å
Source Organism:
Similar Structures:
Biological Unit for 4RN4: monomeric; determined by author and by software (PISA)
Molecular Components in 4RN4
Label Count Molecule
Protein (1 molecule)
Carbonic Anhydrase 2(Gene symbol: CA2)
Molecule annotation
Chemicals (4 molecules)
* Click molecule labels to explore molecular sequence information.

Citing MMDB