Human isozyme

Tempering C., Scozzafava, A., Puccetti, L., and Supuran, C. (2005). Carbonic anhydrase activators X-ray crystal structure of the adduct of human isozyme II with histidine as a platform for the design of stronger activators. Bioorg. Med. Chem. Lett. 15,5136-5141. 

Patients with 11/1-hydroxylase deficiency present with features of androgen excess, including masculinization of female newborns and precocious puberty in male children. There are two human isozymes that are responsible for cortisol and aldosterone synthesis, respectively. The CYP11B1 enzyme (p45011B) converts DOC to corticosterone (B) and 11-deoxycortisol (S or 11-dihydrocortisol) to cortisol (F). It is also capable of 18-hydroxylating DOC but cannot convert to aldosterone. The latter transformation is carried out by CYP11B2 (also known as aldosterone synthase), which encompasses activity for 18-hydroxylation and subsequent 18-oxidation. When CAH is associated with hypertension, deficient lljS-hydroxylase (CYP11B1) is suspected at this time more than ten mutations have been defined in affected individuals [103]. 

There are nine known human isozymes within the UGT1 family and six within the UGT2 family. Polymorphic forms of some of these enzymes are associated with diseases and significant adverse effects to some drugs. 

P. falciparum PNP also proceeds through a TS different than bovine however similar to human isozyme. The TS properties and their interactions in the active site obtained from KIEs analysis provide useful information for inhibitor design. 

Kai M, Wada I, Imai S, Sakane F, Kanoh H (1997) Cloning and characterization of two human isozymes of Mg24-independent phosphatidic acid phosphatase. J Biol Chem 272 24572-24578... 

Crystal structures have been solved for both human isozymes and show that the size of the active site cavity differs between the two enzymes,resulting in the differing substrate specificities. 

Scozzafava, A. Supuran, C.T. (2002b). Carbonic Anhydrase Activators Human Isozyme II is Strongly Activated by Oligopeptides Incorporating the Carboxyterminal Sequence of the Bicarbonate Anion Exchanger AEl. Bioorganic Medicinal Chemistry Letters, 12,1177-1180. 

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