The structural comparison between membrane-associated human carbonic anhydrases provides insights into drug design of selective inhibitors.

Article Details

Citation

Alterio V, Pan P, Parkkila S, Buonanno M, Supuran CT, Monti SM, De Simone G

The structural comparison between membrane-associated human carbonic anhydrases provides insights into drug design of selective inhibitors.

Biopolymers. 2014 Jul;101(7):769-78. doi: 10.1002/bip.22456.

PubMed ID
24374484 [ View in PubMed
]
Abstract

Carbonic anhydrase isoform XIV (CA XIV) is the last member of the human (h) CA family discovered so far, being localized in brain, kidneys, colon, small intestine, urinary bladder, liver, and spinal cord. It has recently been described as a possible drug target for treatment of epilepsy, some retinopathies as well as some skin tumors. Human carbonic anhydrase (hCA) XIV is a membrane-associated protein consisting of an N-terminal extracellular domain, a putative transmembrane region, and a small cytoplasmic tail. In this article, we report the expression, purification, and the crystallographic structure of the entire extracellular domain of this enzyme. The analysis of the structure revealed the typical alpha-CA fold, in which a 10-stranded beta-sheet forms the core of the molecule, while the comparison with all the other membrane associated isoforms (hCAs IV, IX, and XII) allowed to identify the diverse oligomeric arrangement and the sequence and structural differences observed in the region 127-136 as the main factors to consider in the design of selective inhibitors for each one of the membrane associated alpha-CAs.

DrugBank Data that Cites this Article

Polypeptides
NameUniProt ID
Carbonic anhydrase 14Q9ULX7Details