A 5-Class of Carbonic Anhydrase

Roberts et al. reported a 27 kDa monomeric carbonic anhydrase, TWCAl, from the marine diatom Thalassiosira weissflogii (221). X-ray absorption spectroscopy indicated that the catalytic zinc is coordinated by three histidines and a water molecule, similar to the active sites of the a- and y-CAs (222). Also, the active site geometry is similar to that of a-CAs. Based on these results the catalytic mechanism is expected to be similar to that of the cx-class carbonic anhydrases. Tripp et al. (223) proposed that this TWCAl is the prototype of a fourth class carbonic anhydrase designated as 5-class CAs. In the 

A number of papers on some transition-metal model complexes have been reported in the literature to mimic the activity of CA and explore further information on the catalytic mechanism of CA. This aspect has been dealt with in Section IV on formation and aquation/decarboxylation of carbonato complexes. A few more relevant 

Kimura (225) studied a potentially attractive model Zn-complex of [12]aneN3- It confirms to a tetrahedral geometry with a H2O at the fourth coordination site PjZn OH2] and p/ifa of Zn-bound water is 7.3 (25 °C, /=0.1 M NaC104) S4g). X-ray crystal structure 

X-ray cr5 tal structure of Zn [12]aneN3 NCS)2 revealed a five-coordinate TBP which mimics the structure of the NCS adduct of CA (225). Kinetic results demonstrated that NCS and Nj inhibit competitively the catalsdic activity of 4-nitrophenyl acetate (NA) hydrolysis by Zn [12]aneN3 (46b). These results lend support to 

The neutral inhibitors of CA like sulfonamide, such as acetozola-mide, bind to Zn -[12]aneN3 in a 1 1 stoichiometry as determined from 4-NA hydrolysis and isolation of Zn-sulfonamide-pendant [12]aneNa complex. UV-spectral data indicated coordination of sulfonamide anion to Zn -[12]aneN3. The X-ray crystal structure of the Zn-imidazole-pendant [12]aneN3 complex revealed a five-coordinate TBP structure with imidazole N at an equatorial position and a Cl counter ion at an apical position. Neither this complex nor its deprotonated imidazolate form (pi a 10.3) hydrolyzes 4-NA in aqueous solution, indicating the inhibitory action of imidazole similar to that for CA. 

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