7XRQ

The Catalytic Core Structure of Cystathionine beta-Synthase from Candida albicans

Summary for 7XRQ

• Entry DOI: 10.2210/pdb7xrq/pdb
• Descriptor: Cystathionine beta-synthase, PHOSPHATE ION (3 entities in total)
• Functional Keywords: cystathionine beta-synthase, catalytic core center, lyase
• Biological source: Candida albicans (strain SC5314 / ATCC MYA-2876) (Yeast)
• Total number of polymer chains: 2
• Total formula weight: 76629.60

Authors

Lou, H.X.,Yu, H.N.,Chang, W.Q. (deposition date: 2022-05-11, release date: 2023-04-19, Last modification date: 2023-11-29)

Primary citation

Chang, W.,Zhang, M.,Jin, X.,Zhang, H.,Zheng, H.,Zheng, S.,Qiao, Y.,Yu, H.,Sun, B.,Hou, X.,Lou, H.
Inhibition of fungal pathogenicity by targeting the H 2 S-synthesizing enzyme cystathionine beta-synthase.
Sci Adv, 8:eadd5366-eadd5366, 2022

PubMed Abstract: The global emergence of antifungal resistance threatens the limited arsenal of available treatments and emphasizes the urgent need for alternative antifungal agents. Targeting fungal pathogenic functions is an appealing alternative therapeutic strategy. Here, we show that cystathionine β-synthase (CBS), compared with cystathionine γ-lyase, is the major enzyme that synthesizes hydrogen sulfide in the pathogenic fungus . Deletion of CBS leads to deficiencies in resistance to oxidative stress, retarded cell growth, defective hyphal growth, and increased β-glucan exposure, which, together, reduce the pathogenicity of . By high-throughput screening, we identified protolichesterinic acid, a natural molecule obtained from a lichen, as an inhibitor of CBS that neutralizes the virulence of and exhibits therapeutic efficacy in a murine candidiasis model. These findings support the application of CBS as a potential therapeutic target to fight fungal infections.

PubMed: 36525499
DOI: 10.1126/sciadv.add5366

Experimental method

X-RAY DIFFRACTION (2.501 Å)