Recent advances in structural studies of the carbonic anhydrase family: the crystal structure of human CA IX and CA XIII.
The carbonic anhydrase (CA) family has recently become an important target for the drug design of inhibitors with potential use as diagnostic and therapeutic tools. However, given the high degree of sequence and structure similarity among the different CA isoforms, no CA-directed drug developed so far has displayed selectivity for a specific isozyme. Since X-Ray crystallography is a very useful tool for the rational drug design of selective enzyme inhibitors, in recent years extensive research efforts have been devoted to the structural studies of all catalytically active &alpha;-CA isoforms, with the consequent resolution of the crystallographic structures of nearly all such enzyme isoforms. In this paper we review the progress that has recently been made in this field. In particular, we summarize the main structural features of hCA XIII and hCA IX, the most recently characterized human CA isoforms, and recapitulate how 3D structures of these enzymes, together with kinetic experiments, have been used either to deepen our knowledge on the structural features responsible of the catalytic properties of this protein family or to obtain important information for the rational drug design of inhibitors with better selectivity properties.
Supuran
Claudiu T
CT
Università degli Studi di Firenze, Laboratorio di Chimica Bioinorganica, Via della Lastruccia 3, Sesto Fiorentino, Florence, Italy. claudiu.supuran@unifi.it
Di Fiore
Anna
A
Alterio
Vincenzo
V
Monti
Simona Maria
SM
De Simone
Giuseppina
G
D000951:Antigens, Neoplasm / Q000737:chemistry* / Q000187:drug effects / Q000378:metabolism; D000071231:Carbonic Anhydrase IX; D002257:Carbonic Anhydrase Inhibitors / Q000494:pharmacology; D002256:Carbonic Anhydrases / Q000737:chemistry* / Q000187:drug effects / Q000378:metabolism; D018360:Crystallography, X-Ray / Q000379:methods*; D015195:Drug Design; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000187:drug effects; D008958:Models, Molecular; D020836:Protein Structure, Quaternary
D000951:Antigens, Neoplasm; D002257:Carbonic Anhydrase Inhibitors; D007527:Isoenzymes; C483903:CA13 protein, human; C089226:CA9 protein, human; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases