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Characterization of CA XIII, a novel member of the carbonic anhydrase isozyme family.

Lehtonen, Jonna; Shen, Bairong; Vihinen, Mauno LU ; Casini, Angela; Scozzafava, Andrea; Supuran, Claudiu T; Parkkila, Anna-Kaisa; Saarnio, Juha; Kivelä, Antti J and Waheed, Abdul, et al. (2004) In Journal of Biological Chemistry 279(4). p.2719-2727
Abstract
The carbonic anhydrase (CA) gene family has been reported to consist of at least 11 enzymatically active members and a few inactive homologous proteins. Recent analyses of human and mouse databases provided evidence that human and mouse genomes contain genes for still another novel CA isozyme hereby named CA XIII. In the present study, we modeled the structure of human CA XIII. This model revealed a globular molecule with high structural similarity to cytosolic isozymes, CA I, II, and III. Recombinant mouse CA XIII showed catalytic activity similar to those of mitochondrial CA V and cytosolic CA I, with k(cat)/K(m) of 4.3 x 10(7) m(-1) s(-1), and k(cat) of 8.3 x 10(4) s(-1). It is very susceptible to inhibition by sulfonamide and anionic... (More)
The carbonic anhydrase (CA) gene family has been reported to consist of at least 11 enzymatically active members and a few inactive homologous proteins. Recent analyses of human and mouse databases provided evidence that human and mouse genomes contain genes for still another novel CA isozyme hereby named CA XIII. In the present study, we modeled the structure of human CA XIII. This model revealed a globular molecule with high structural similarity to cytosolic isozymes, CA I, II, and III. Recombinant mouse CA XIII showed catalytic activity similar to those of mitochondrial CA V and cytosolic CA I, with k(cat)/K(m) of 4.3 x 10(7) m(-1) s(-1), and k(cat) of 8.3 x 10(4) s(-1). It is very susceptible to inhibition by sulfonamide and anionic inhibitors, with inhibition constants of 17 nm for acetazolamide, a clinically used sulfonamide, and of 0.25 microm, for cyanate, respectively. Using panels of cDNAs we evaluated human and mouse CA13 gene expression in a number of different tissues. In human tissues, positive signals were identified in the thymus, small intestine, spleen, prostate, ovary, colon, and testis. In mouse, positive tissues included the spleen, lung, kidney, heart, brain, skeletal muscle, and testis. We also investigated the cellular and subcellular localization of CA XIII in human and mouse tissues using an antibody raised against a polypeptide of 14 amino acids common for both human and mouse orthologues. Immunohistochemical staining showed a unique and widespread distribution pattern for CA XIII compared with the other cytosolic CA isozymes. In conclusion, the predicted amino acid sequence, structural model, distribution, and activity data suggest that CA XIII represents a novel enzyme, which may play important physiological roles in several organs. (Less)
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subject
keywords
Carbonic Anhydrases: analysis, Carbonic Anhydrases: genetics, Carbonic Anhydrases: metabolism, Isoenzymes: analysis, Isoenzymes: genetics, Isoenzymes: metabolism
in
Journal of Biological Chemistry
volume
279
issue
4
pages
2719 - 2727
publisher
ASBMB
external identifiers
  • pmid:14600151
  • scopus:9144220136
ISSN
1083-351X
DOI
10.1074/jbc.M308984200
language
English
LU publication?
no
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0360b88d-c684-4bff-97e5-abaf5aebbaab (old id 3635533)
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http://www.ncbi.nlm.nih.gov/pubmed/14600151?dopt=Abstract
date added to LUP
2013-06-12 16:03:36
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2017-11-12 04:08:12
@article{0360b88d-c684-4bff-97e5-abaf5aebbaab,
  abstract     = {The carbonic anhydrase (CA) gene family has been reported to consist of at least 11 enzymatically active members and a few inactive homologous proteins. Recent analyses of human and mouse databases provided evidence that human and mouse genomes contain genes for still another novel CA isozyme hereby named CA XIII. In the present study, we modeled the structure of human CA XIII. This model revealed a globular molecule with high structural similarity to cytosolic isozymes, CA I, II, and III. Recombinant mouse CA XIII showed catalytic activity similar to those of mitochondrial CA V and cytosolic CA I, with k(cat)/K(m) of 4.3 x 10(7) m(-1) s(-1), and k(cat) of 8.3 x 10(4) s(-1). It is very susceptible to inhibition by sulfonamide and anionic inhibitors, with inhibition constants of 17 nm for acetazolamide, a clinically used sulfonamide, and of 0.25 microm, for cyanate, respectively. Using panels of cDNAs we evaluated human and mouse CA13 gene expression in a number of different tissues. In human tissues, positive signals were identified in the thymus, small intestine, spleen, prostate, ovary, colon, and testis. In mouse, positive tissues included the spleen, lung, kidney, heart, brain, skeletal muscle, and testis. We also investigated the cellular and subcellular localization of CA XIII in human and mouse tissues using an antibody raised against a polypeptide of 14 amino acids common for both human and mouse orthologues. Immunohistochemical staining showed a unique and widespread distribution pattern for CA XIII compared with the other cytosolic CA isozymes. In conclusion, the predicted amino acid sequence, structural model, distribution, and activity data suggest that CA XIII represents a novel enzyme, which may play important physiological roles in several organs.},
  author       = {Lehtonen, Jonna and Shen, Bairong and Vihinen, Mauno and Casini, Angela and Scozzafava, Andrea and Supuran, Claudiu T and Parkkila, Anna-Kaisa and Saarnio, Juha and Kivelä, Antti J and Waheed, Abdul and Sly, William S and Parkkila, Seppo},
  issn         = {1083-351X},
  keyword      = {Carbonic Anhydrases: analysis,Carbonic Anhydrases: genetics,Carbonic Anhydrases: metabolism,Isoenzymes: analysis,Isoenzymes: genetics,Isoenzymes: metabolism},
  language     = {eng},
  number       = {4},
  pages        = {2719--2727},
  publisher    = {ASBMB},
  series       = {Journal of Biological Chemistry},
  title        = {Characterization of CA XIII, a novel member of the carbonic anhydrase isozyme family.},
  url          = {http://dx.doi.org/10.1074/jbc.M308984200},
  volume       = {279},
  year         = {2004},
}