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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2020.1
- 수록면
- 831 - 840 (10page)
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The β-class of carbonic anhydrases (β-CAs) are zinc metalloenzymes widely distributed in the fungal kingdom that play essential roles in growth, survival, differentiation, and virulence by catalyzing the reversible interconversion of carbon dioxide (CO2) and bicarbonate (HCO3?). Herein, we report the biochemical and crystallographic characterization of the β-CA CafA from the fungal pathogen Aspergillus fumigatus, the main causative agent of invasive aspergillosis. CafA exhibited apparent in vitro CO2 hydration activity in neutral to weak alkaline conditions, but little activity at acidic pH. The high-resolution crystal structure of CafA revealed a tetramer comprising a dimer of dimers, in which the catalytic zinc ion is tetrahedrally coordinated by three conserved residues (C119, H175, C178) and an acetate anion presumably acquired from the crystallization solution, indicating a freely accessible ″open″ conformation. Furthermore, knowledge of the structure of CafA in complex with the potent inhibitor acetazolamide, together with its functional intolerance of nitrate (NO3?) ions, could be exploited to develop new antifungal agents for the treatment of invasive aspergillosis.
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참고문헌 (58)
참고문헌 신청
Adams, P. D. / 2010 / PHENIX: a comprehensive Python-based system for macromolecular structure solution / Acta Crystallogr. D Biol. Crystallogr 66:213~221
Alterio, V. / 2009 / Crystal structure of the catalytic domain of the tumor-associated human carbonic anhydrase IX / Proc. Natl. Acad. Sci. U. S. A. 106:16233~16238
Amich, J. / 2010 / Aspergillus fumigatus survival in alkaline and extreme zinc-limiting environments relies on the induction of a zinc homeostasis system encoded by the zrfC and aspf2 genes / Eukaryot. Cell 9:424~437
Bahn, Y. S. / 2005 / Carbonic anhydrase and CO2 sensing during Cryptococcus neoformans growth, differentiation, and virulence / Curr. Biol 15:2013~2020
Capasso, C. / 2012 / Biochemical properties of a novel and highly thermostable bacterial alpha-carbonic anhydrase from Sulfurihydrogenibium yellowstonense YO3AOP1 / J. Enzyme Inhib. Med. Chem 27:892~897
Alterio, V. / 2009 / Crystal structure of the catalytic domain of the tumor-associated human carbonic anhydrase IX / Proc. Natl. Acad. Sci. U. S. A. 106:16233~16238
Amich, J. / 2010 / Aspergillus fumigatus survival in alkaline and extreme zinc-limiting environments relies on the induction of a zinc homeostasis system encoded by the zrfC and aspf2 genes / Eukaryot. Cell 9:424~437
Bahn, Y. S. / 2005 / Carbonic anhydrase and CO2 sensing during Cryptococcus neoformans growth, differentiation, and virulence / Curr. Biol 15:2013~2020
Capasso, C. / 2012 / Biochemical properties of a novel and highly thermostable bacterial alpha-carbonic anhydrase from Sulfurihydrogenibium yellowstonense YO3AOP1 / J. Enzyme Inhib. Med. Chem 27:892~897
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