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IBBR publication #1316

Acatalytic Carbonic Anhydrases (CAs VIII, X, XI)

Supuran CT, Capasso C

In: “Carbonic Anhydrases as Biocatalysts: From Theory to Medical and Industrial Applications”. pp. 239-245. (2015)
doi: 10.1016/B978-0-444-63258-6.00013-5
URL: http://www.scopus.com/inward/record.url?eid=2-s2.0-84943578225&partne...

Carbonic anhydrases (CAs) are found in almost all organisms and are zinc metalloenzymes that catalyze the interconversion of CO2 and HCO3 -. In mammals, α-CA gene family consists of 13 isoforms that are catalytically active and 3 isoforms that are catalytically inactive. Due to high sequence and structural similarity with the active α-CAs, these proteins have been designated as CA-related proteins (CARPs). Thus, the three mammalian inactive CAs VIII, X, and XI are also named as CARP VIII, CARP X, and CARP XI. Despite the high degree of homology, these proteins distinguish themselves from the catalytically active CAs by a salient feature: they lack one, two, or all three zinc protein ligands from the enzyme active site. CA VIII has been initially identified in the brain, and, lately, its expression has also been demonstrated in liver, lung, heart, gut, thymus, and kidneys. CA X and XI are also predominantly found in the brain. CA VIII and CA XI have been reported to be overexpressed in tumors such as lung and colorectal cancer (CA VIII) or in gastrointestinal stromal tumors (CA XI). Mutation of amino acid residues 94, 96, and 119 to histidine(s) in these acatalytic proteins restored the zinc-binding and catalytic activity for the hydration reaction of CO2 to bicarbonate. These "restored enzymes" showed a high hydration activity and good inhibition toward inorganic anions such as sulfamide. The phylogenetic analysis of CARPs suggested that their genes are more ancient with respect to those of the catalytic α-CAs.

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