Cell Reports (Jul 2023)
Hydrogen sulfide functions as a micro-modulator bound at the copper active site of Cu/Zn-SOD to regulate the catalytic activity of the enzyme
- Dong-Dong Wu,
- Sheng Jin,
- Ruo-Xiao Cheng,
- Wen-Jie Cai,
- Wen-Long Xue,
- Qing-Qing Zhang,
- Le-Jie Yang,
- Qi Zhu,
- Meng-Yao Li,
- Ge Lin,
- Yi-Zhen Wang,
- Xue-Pan Mu,
- Yu Wang,
- Igor Ying Zhang,
- Qi Zhang,
- Ying Chen,
- Sheng-Yang Cai,
- Bo Tan,
- Ye Li,
- Yun-Qian Chen,
- Pu-Juan Zhang,
- Chen Sun,
- Yue Yin,
- Ming-Jie Wang,
- Yi-Zhun Zhu,
- Bei-Bei Tao,
- Jia-Hai Zhou,
- Wei-Xue Huang,
- Yi-Chun Zhu
Affiliations
- Dong-Dong Wu
- Shanghai Key Laboratory of Bioactive Small Molecules, Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University Shanghai Medical College, Shanghai 200032, China; School of Stomatology, Henan University, Kaifeng, Henan 475004, China; Henan International Joint Laboratory for Nuclear Protein Regulation, School of Basic Medical Sciences, Henan University, Kaifeng, Henan 475004, China
- Sheng Jin
- Shanghai Key Laboratory of Bioactive Small Molecules, Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University Shanghai Medical College, Shanghai 200032, China; Department of Physiology, Hebei Medical University, 361 Zhongshan Road, Shijiazhuang 050017, China
- Ruo-Xiao Cheng
- State Key Laboratory of Chemical Biology, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032, China
- Wen-Jie Cai
- Shanghai Key Laboratory of Bioactive Small Molecules, Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University Shanghai Medical College, Shanghai 200032, China; School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai 200093, China; Corresponding author
- Wen-Long Xue
- Shanghai Key Laboratory of Bioactive Small Molecules, Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University Shanghai Medical College, Shanghai 200032, China
- Qing-Qing Zhang
- Shanghai Key Laboratory of Bioactive Small Molecules, Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University Shanghai Medical College, Shanghai 200032, China
- Le-Jie Yang
- Shanghai Key Laboratory of Bioactive Small Molecules, Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University Shanghai Medical College, Shanghai 200032, China
- Qi Zhu
- Shanghai Key Laboratory of Bioactive Small Molecules, Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University Shanghai Medical College, Shanghai 200032, China
- Meng-Yao Li
- Shanghai Key Laboratory of Bioactive Small Molecules, Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University Shanghai Medical College, Shanghai 200032, China
- Ge Lin
- Shanghai Key Laboratory of Bioactive Small Molecules, Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University Shanghai Medical College, Shanghai 200032, China
- Yi-Zhen Wang
- Henan International Joint Laboratory for Nuclear Protein Regulation, School of Basic Medical Sciences, Henan University, Kaifeng, Henan 475004, China
- Xue-Pan Mu
- Shanghai Key Laboratory of Bioactive Small Molecules, Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University Shanghai Medical College, Shanghai 200032, China
- Yu Wang
- Shanghai Synchrotron Radiation Facility, Shanghai Advanced Research Institute, Chinese Academy of Sciences, Shanghai 201204, China
- Igor Ying Zhang
- Department of Chemistry, Fudan University, Shanghai 200438, China
- Qi Zhang
- Department of Chemistry, Fudan University, Shanghai 200438, China
- Ying Chen
- Shanghai Key Laboratory of Bioactive Small Molecules, Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University Shanghai Medical College, Shanghai 200032, China
- Sheng-Yang Cai
- Shanghai Key Laboratory of Bioactive Small Molecules, Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University Shanghai Medical College, Shanghai 200032, China
- Bo Tan
- Clinical Pharmacokinetic Laboratory, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
- Ye Li
- Shanghai Key Laboratory of Bioactive Small Molecules, Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University Shanghai Medical College, Shanghai 200032, China
- Yun-Qian Chen
- Shanghai Key Laboratory of Atmospheric Particle Pollution and Prevention (LAP3), Department of Environmental Science & Engineering, Fudan University, Shanghai 200438, China
- Pu-Juan Zhang
- State Key Laboratory of Chemical Biology, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032, China
- Chen Sun
- Shanghai Key Laboratory of Bioactive Small Molecules, Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University Shanghai Medical College, Shanghai 200032, China
- Yue Yin
- National Facility for Protein Science in Shanghai, Shanghai Advanced Research Institute, Chinese Academy of Science, Shanghai 201210, China
- Ming-Jie Wang
- Shanghai Key Laboratory of Bioactive Small Molecules, Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University Shanghai Medical College, Shanghai 200032, China
- Yi-Zhun Zhu
- Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai 200433, China; State Key Laboratory of Quality Research in Chinese Medicine and School of Pharmacy, Macau University of Science and Technology, Avenida WaiLong, Taipa, Macau 999078, China
- Bei-Bei Tao
- Shanghai Key Laboratory of Bioactive Small Molecules, Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University Shanghai Medical College, Shanghai 200032, China
- Jia-Hai Zhou
- CAS Key Laboratory of Quantitative Engineering Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China; Corresponding author
- Wei-Xue Huang
- State Key Laboratory of Chemical Biology, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032, China; Corresponding author
- Yi-Chun Zhu
- Shanghai Key Laboratory of Bioactive Small Molecules, Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University Shanghai Medical College, Shanghai 200032, China; Corresponding author
- Journal volume & issue
-
Vol. 42,
no. 7
p. 112750
Abstract
Summary: The present study examines whether there is a mechanism beyond the current concept of post-translational modifications to regulate the function of a protein. A small gas molecule, hydrogen sulfide (H2S), was found to bind at active-site copper of Cu/Zn-SOD using a series of methods including radiolabeled binding assay, X-ray absorption near-edge structure (XANES), and crystallography. Such an H2S binding enhanced the electrostatic forces to guide the negatively charged substrate superoxide radicals to the catalytic copper ion, changed the geometry and energy of the frontier molecular orbitals of the active site, and subsequently facilitated the transfer of an electron from the superoxide radical to the catalytic copper ion and the breakage of the copper-His61 bridge. The physiological relevance of such an H2S effect was also examined in both in vitro and in vivo models where the cardioprotective effects of H2S were dependent on Cu/Zn-SOD.
