Crystal structure of human carbonic anhydrase XIII and its complex with the inhibitor acetazolamide.
The cytosolic isoform XIII is a recently discovered member of the human carbonic anhydrase (hCA, EC 4.2.1.1) family. It is selectively expressed among other tissues in the reproductive organs, where it may control pH and ion balance regulation, ensuring thus proper fertilization conditions. The authors report here the X-ray crystallographic structure of this isozyme in the unbound state and in complex with a classical sulfonamide inhibitor, namely acetazolamide. A detailed comparison of the obtained structural data with those already reported for other CA isozymes provides novel insights into the catalytic properties of the members of this protein family. On the basis of the inhibitory properties of acetazolamide against various cytosolic/transmembrane isoforms and the structural differences detected within the active site of the various CA isoforms, further prospects for the design of isozyme-specific CA inhibitors are here proposed.
Di Fiore
Anna
A
Istituto di Biostrutture e Bioimmagini-CNR, 80134 Naples, Italy.
Monti
Simona Maria
SM
Hilvo
Mika
M
Parkkila
Seppo
S
Romano
Vincenza
V
Scaloni
Andrea
A
Pedone
Carlo
C
Scozzafava
Andrea
A
Supuran
Claudiu T
CT
De Simone
Giuseppina
G
D000086:Acetazolamide / Q000737:chemistry* / Q000378:metabolism*; D000818:Animals; D001665:Binding Sites; D002257:Carbonic Anhydrase Inhibitors / Q000737:chemistry* / Q000378:metabolism*; D002256:Carbonic Anhydrases / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism*; D018360:Crystallography, X-Ray; D004926:Escherichia coli; D029968:Escherichia coli Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism; D006801:Humans; D007527:Isoenzymes / Q000737:chemistry / Q000378:metabolism; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism
D002257:Carbonic Anhydrase Inhibitors; D029968:Escherichia coli Proteins; D007527:Isoenzymes; D011994:Recombinant Proteins; C483903:CA13 protein, human; D002256:Carbonic Anhydrases; D000086:Acetazolamide