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Crystal Structure of β-Carbonic Anhydrase CafA from the Fungal Pathogen Aspergillus fumigatus

Molecules and Cells 2020년 43권 9호 p.831 ~ 840
김수빈, Yeon Jung-Yoon, Sung Jong-Min, Jin Mi-Sun,
소속 상세정보
김수빈 ( Kim Su-Bin ) - Gwangju Institute of Science and Technology School of Life Sciences
 ( Yeon Jung-Yoon ) - Gwangju Institute of Science and Technology School of Life Sciences
 ( Sung Jong-Min ) - Gwangju Institute of Science and Technology School of Life Sciences
 ( Jin Mi-Sun ) - Gwangju Institute of Science and Technology School of Life Sciences

Abstract


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.

키워드

β-class carbonic anhydrase; Aspergillus fumigatus; CafA; X-ray crystallography; zinc metalloenzyme

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