Carbonic anhydrase 2

Definition:

Catalyzes the reversible hydration of carbon dioxide. Can also hydrate cyanamide to urea. Stimulates the chloride-bicarbonate exchange activity of SLC26A6. Essential for bone resorption and osteoclast differentiation. Involved in the regulation of fluid secretion into the anterior chamber of the eye. Contributes to intracellular pH regulation in the duodenal upper villous epithelium during proton-coupled peptide absorption.

References:

[1]. Anna Di Fiore, et al. Carbonic anhydrase inhibitors: binding of an antiglaucoma glycosyl-sulfanilamide derivative to human isoform II and its consequences for the drug design of enzyme inhibitors incorporating sugar moieties. Bioorg Med Chem Lett. 2007 Mar 15;17(6):1726-31. [Content Brief]

[2]. Gul N Shah, et al. Carbonic anhydrase II deficiency syndrome (osteopetrosis with renal tubular acidosis and brain calcification): novel mutations in CA2 identified by direct sequencing expand the opportunity for genotype-phenotype correlation. Hum Mutat. 2004 Sep;24(3):272. [Content Brief]

[3]. Claudia Temperini, et al. Carbonic anhydrase inhibitors: the X-ray crystal structure of the adduct of N-hydroxysulfamide with isozyme II explains why this new zinc binding function is effective in the design of potent inhibitors. Bioorg Med Chem Lett. 2007 May 15;17(10):2795-801. [Content Brief]

[4]. Deepa Bhatt, et al. Proton transfer in a Thr200His mutant of human carbonic anhydrase II. Proteins. 2005 Nov 1;61(2):239-45. [Content Brief]

[5]. Bernardo V Alvarez, et al. Metabolon disruption: a mechanism that regulates bicarbonate transport. EMBO J. 2005 Jul 20;24(14):2499-511. [Content Brief]

[6]. J A Ippolito, et al. Structure of an engineered His3Cys zinc binding site in human carbonic anhydrase II. Biochemistry. 1993 Sep 28;32(38):9901-5. [Content Brief]

[7]. J F Krebs, et al. Conformational mobility of His-64 in the Thr-200----Ser mutant of human carbonic anhydrase II. Biochemistry. 1991 Sep 24;30(38):9153-60. [Content Brief]

[8]. Chingkuang Tu, et al. Kinetic analysis of multiple proton shuttles in the active site of human carbonic anhydrase. J Biol Chem. 2002 Oct 11;277(41):38870-6. [Content Brief]

[9]. Y Xue, et al. Crystallographic analysis of Thr-200-->His human carbonic anhydrase II and its complex with the substrate, HCO3-. Proteins. 1993 Jan;15(1):80-7. [Content Brief]

[10]. Y Xue, et al. Structural analysis of the zinc hydroxide-Thr-199-Glu-106 hydrogen-bond network in human carbonic anhydrase II. Proteins. 1993 Sep;17(1):93-106. [Content Brief]

[11]. J A Ippolito, et al. Structure-assisted redesign of a protein-zinc-binding site with femtomolar affinity. Proc Natl Acad Sci U S A. 1995 May 23;92(11):5017-21. [Content Brief]

[12]. Jiayin Zheng, et al. Role of hydrophilic residues in proton transfer during catalysis by human carbonic anhydrase II. Biochemistry. 2008 Nov 18;47(46):12028-36. [Content Brief]

[13]. F Briganti, et al. Carbonic anhydrase catalyzes cyanamide hydration to urea: is it mimicking the physiological reaction?. J Biol Inorg Chem. 1999 Oct;4(5):528-36. [Content Brief]

[14]. Chu-Young Kim, et al. Structural aspects of isozyme selectivity in the binding of inhibitors to carbonic anhydrases II and IV. J Med Chem. 2002 Feb 14;45(4):888-93. [Content Brief]

[15]. J F Krebs, et al. Structural and functional importance of a conserved hydrogen bond network in human carbonic anhydrase II. J Biol Chem. 1993 Dec 25;268(36):27458-66. [Content Brief]

[16]. D Duda, et al. Structural and kinetic analysis of the chemical rescue of the proton transfer function of carbonic anhydrase II. Biochemistry. 2001 Feb 13;40(6):1741-8. [Content Brief]

[17]. A Guerri, et al. Mechanism of cyanamide hydration catalyzed by carbonic anhydrase II suggested by cryogenic X-ray diffraction. Biochemistry. 2000 Oct 10;39(40):12391-7. [Content Brief]

[18]. S K Nair, et al. Structural consequences of hydrophilic amino acid substitutions in the hydrophobic pocket of human carbonic anhydrase II. Biochemistry. 1993 May 4;32(17):4506-14. [Content Brief]

[19]. N B Tweedy, et al. Structure and energetics of a non-proline cis-peptidyl linkage in a proline-202-->alanine carbonic anhydrase II variant. Biochemistry. 1993 Oct 19;32(41):10944-9. [Content Brief]

[20]. Matthew D Lloyd, et al. First crystal structures of human carbonic anhydrase II in complex with dual aromatase-steroid sulfatase inhibitors. Biochemistry. 2005 May 10;44(18):6858-66. [Content Brief]

[21]. S K Nair, et al. Altering the mouth of a hydrophobic pocket. Structure and kinetics of human carbonic anhydrase II mutants at residue Val-121. J Biol Chem. 1991 Sep 15;266(26):17320-5. [Content Brief]

[22]. Matthew D Lloyd, et al. Crystal structure of human carbonic anhydrase II at 1.95 A resolution in complex with 667-coumate, a novel anti-cancer agent. Biochem J. 2005 Feb 1;385(Pt 3):715-20. [Content Brief]

[23]. Zoë Fisher, et al. Structural and kinetic characterization of active-site histidine as a proton shuttle in catalysis by human carbonic anhydrase II. Biochemistry. 2005 Feb 1;44(4):1097-105. [Content Brief]

[24]. F Briganti, et al. Carbonic anhydrase activators: X-ray crystallographic and spectroscopic investigations for the interaction of isozymes I and II with histamine. Biochemistry. 1997 Aug 26;36(34):10384-92. [Content Brief]

[25]. Shenghua Huang, et al. Organization of an efficient carbonic anhydrase: implications for the mechanism based on structure-function studies of a T199P/C206S mutant. Biochemistry. 2002 Jun 18;41(24):7628-35. [Content Brief]

[26]. S Mangani, et al. Crystallographic studies of the binding of protonated and unprotonated inhibitors to carbonic anhydrase using hydrogen sulphide and nitrate anions. Eur J Biochem. 1992 Dec 15;210(3):867-71. [Content Brief]

[27]. C C Huang, et al. Reversal of the hydrogen bond to zinc ligand histidine-119 dramatically diminishes catalysis and enhances metal equilibration kinetics in carbonic anhydrase II. Biochemistry. 1996 Mar 19;35(11):3439-46. [Content Brief]

[28]. C A Lesburg, et al. Histidine --> carboxamide ligand substitutions in the zinc binding site of carbonic anhydrase II alter metal coordination geometry but retain catalytic activity. Biochemistry. 1997 Dec 16;36(50):15780-91. [Content Brief]

[29]. Claudia Temperini, et al. Carbonic anhydrase activators: X-ray crystal structure of the adduct of human isozyme II with L-histidine as a platform for the design of stronger activators. Bioorg Med Chem Lett. 2005 Dec 1;15(23):5136-41. [Content Brief]

[30]. S Zoë Fisher, et al. Speeding up proton transfer in a fast enzyme: kinetic and crystallographic studies on the effect of hydrophobic amino acid substitutions in the active site of human carbonic anhydrase II. Biochemistry. 2007 Mar 27;46(12):3803-13. [Content Brief]

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