Structural Analysis of an l -Cysteine Desulfurase from an Ssp DNA Phosphorothioation System

Author:

Liu Liqiong1234,Jiang Susu34,Xing Mai34,Chen Chao234,Lai Chongde5,Li Na6,Liu Guangfeng6,Wu Dan3,Gao Haiyan3,Hong Liang7,Tan Pan7,Chen Shi234,Deng Zixin13,Wu Geng1,Wang Lianrong234

Affiliation:

1. State Key Laboratory of Microbial Metabolism, School of Life Sciences and Biotechnology, Joint International Research Laboratory of Metabolic & Developmental Sciences, Shanghai Jiao Tong University, Shanghai, China

2. Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, China

3. Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Ministry of Education, School of Pharmaceutical Sciences, Wuhan University, Wuhan, China

4. Department of Neurosurgery, Zhongnan Hospital, Wuhan University, Wuhan, China

5. Jiangxi Engineering Laboratory for the Development and Utilization of Agricultural Microbial Resources, College of Bioscience and Bioengineering, Jiangxi Agricultural University, Nanchang, China

6. National Facility for Protein Science Shanghai, Zhangjiang Lab, Shanghai, China

7. School of Physics and Astronomy, Shanghai Jiao Tong University, Shanghai, China

Abstract

Apart from its roles in Fe-S cluster assembly, tRNA thiolation, and sulfur-containing cofactor biosynthesis, cysteine desulfurase serves as a sulfur donor in the DNA PT modification, in which a sulfur atom substitutes a nonbridging oxygen in the DNA phosphodiester backbone. The initial sulfur mobilization from l -cysteine is catalyzed by the SspA cysteine desulfurase in the SspABCD-mediated DNA PT modification system. By determining the crystal structure of SspA, the study presents the molecular mechanism that SspA employs to recognize its cysteine substrate and PLP cofactor. To overcome the long distance (8.9 Å) between the catalytic Cys314 and the cysteine substrate, a conformational change occurs to bring Cys314 to the vicinity of the substrate, allowing for nucleophilic attack.

Funder

China National Key Research and Development Program

National Natural Science Foundation of China

Publisher

American Society for Microbiology

Subject

Virology,Microbiology

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