Structural analysis of substrate recognition loop flexibility in D-arabinose dehydrogenase from Candida auris.

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Tác giả: Meng Dan, Zhang Jie, Ki Hyun Nam, Bai Xue, Xu Yongbin

Ngôn ngữ: eng

Ký hiệu phân loại:

Thông tin xuất bản: United States : Biochemical and biophysical research communications , 2025

Mô tả vật lý:

Bộ sưu tập: NCBI

ID: 710988

Candida auris is an emerging fungal pathogen that poses a significant threat to global health due to its multidrug resistance and ability to persist in healthcare settings. A key factor contributing to its survival and virulence is its capacity to combat oxidative stress, a process primarily driven by oxidative stress-related enzymes. One such enzyme, d-arabinose dehydrogenase from C. auris (CaAldO), plays a crucial role in the biosynthesis of d-erythroascorbic acid (EASC), an essential antioxidant that shields fungal cells from oxidative damage. CaAldO catalyzes the oxidation of d-arabinose to D-arabinono-1,5-lactone, a key precursor in EASC synthesis, thereby enhancing the oxidative stress resistance of C. auris. To elucidate its structural features, we determined the high-resolution crystal structure of CaAldO at 1.95 Å. Its cofactor-binding pocket is formed by four loop regions within the TIM-barrel fold. Notably, Loops A and C in the substrate-binding pocket exhibit significant flexibility, facilitating the transition between the open and closed conformations of the cofactor-binding pocket of CaAldO. A structural comparison of CaAldO with its homolog ScAra1 revealed notable differences in the length and conformation of the substrate recognition loops, as well as variations in the cofactor-binding pocket. These findings enhance our understanding of the unique structural properties of CaAldO and offer insights into developing novel antifungal strategies targeting C. auris.
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