4.7 Article

Structural and Biochemical Characterization Reveals LysGH15 as an Unprecedented EF-Hand-Like Calcium-Binding Phage Lysin

期刊

PLOS PATHOGENS
卷 10, 期 5, 页码 -

出版社

PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.ppat.1004109

关键词

-

资金

  1. National Natural Science Foundation of China [31130072]
  2. Ministry of Education
  3. Jilin University

向作者/读者索取更多资源

The lysin LysGH15, which is derived from the staphylococcal phage GH15, demonstrates a wide lytic spectrum and strong lytic activity against methicillin-resistant Staphylococcus aureus (MRSA). Here, we find that the lytic activity of the full-length LysGH15 and its CHAP domain is dependent on calcium ions. To elucidate the molecular mechanism, the structures of three individual domains of LysGH15 were determined. Unexpectedly, the crystal structure of the LysGH15 CHAP domain reveals an EF-hand-like calcium-binding site near the Cys-His-Glu-Asn quartet active site groove. To date, the calcium-binding site in the LysGH15 CHAP domain is unique among homologous proteins, and it represents the first reported calcium-binding site in the CHAP family. More importantly, the calcium ion plays an important role as a switch that modulates the CHAP domain between the active and inactive states. Structure-guided mutagenesis of the amidase-2 domain reveals that both the zinc ion and E282 are required in catalysis and enable us to propose a catalytic mechanism. Nuclear magnetic resonance (NMR) spectroscopy and titration-guided mutagenesis identify residues (e. g., N404, Y406, G407, and T408) in the SH3b domain that are involved in the interactions with the substrate. To the best of our knowledge, our results constitute the first structural information on the biochemical features of a staphylococcal phage lysin and represent a pivotal step forward in understanding this type of lysin.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.7
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

Article Chemistry, Physical

H-Bonding Networks Dictate the Molecular Mechanism of H2O2 Activation by P450

Xuan Zhang, Yiping Jiang, Qianqian Chen, Sheng Dong, Yingang Feng, Zhiqi Cong, Sason Shaik, Binju Wang

Summary: Understanding the molecular basis of controlled H2O2 activation is crucial for peroxide-driven catalysis by metalloenzymes. This study demonstrates the significant influence of substrates and dual-functional small molecules (DFSM) on H2O2 activation, with hydrogen bonding networks playing key roles in dictating the process.

ACS CATALYSIS (2021)

Correction Biophysics

Resonance assignments for the tandem PWWP-ARID domains of human RBBP1 (vol 13, pg 177, 2019)

Weibin Gong, Xingzhe Yao, Qihui Liang, Yufeng Tong, Sarah Perrett, Yingang Feng

BIOMOLECULAR NMR ASSIGNMENTS (2022)

Article Biochemistry & Molecular Biology

Cargo Recognition Mechanisms of Yeast Myo2 Revealed by AlphaFold2-Powered Protein Complex Prediction

Yong Liu, Lingxuan Li, Cong Yu, Fuxing Zeng, Fengfeng Niu, Zhiyi Wei

Summary: The study predicts the complex structures of Myo2-GTD and its cargo adaptors using ColabFold and summarizes the versatile cargo-recognition mechanisms of Myo2 by comparing the interaction details of multiple complexes. The research provides an efficient solution for studying protein-protein interactions.

BIOMOLECULES (2022)

Article Chemistry, Medicinal

Discovery of a cysteine-rich peptide with glycation modification from Achyranthes bidentata Blume

Meixi He, Yingang Feng, Yi Wang, Mengchun Cheng, Xiaozhe Zhang, Lihua Zhang

Summary: In this study, a cysteine-rich glycation peptide, termed glycation-bidentatide (Gly-BTP), was discovered in the Chinese herb Achyranthes bidentata Blume. Cell bioactivity assay results suggested that Gly-BTP might have potential therapeutic effects and provide neuroprotection in NMDA-induced HT22 murine hippocampal neuronal cells. The discovery of Gly-BTP contributes to the understanding of the role of CRPs in neuroprotection.

FITOTERAPIA (2022)

Correction Biochemistry & Molecular Biology

Correction: Structural basis for the DNA-binding activity of human ARID4B Tudor domain

Jie Ren, Hongwei Yao, Wanhui Hu, Sarah Perrett, Weibin Gong, Yingang Feng

JOURNAL OF BIOLOGICAL CHEMISTRY (2022)

Article Chemistry, Multidisciplinary

Regiodivergent and Enantioselective Hydroxylation of C-H bonds by Synergistic Use of Protein Engineering and Exogenous Dual-Functional Small Molecules

Jie Chen, Sheng Dong, Wenhan Fang, Yiping Jiang, Zhifeng Chen, Xiangquan Qin, Cong Wang, Haifeng Zhou, Longyi Jin, Yingang Feng, Binju Wang, Zhiqi Cong

Summary: We report the selective hydroxylation of alkylbenzenes using an engineered P450 peroxygenase driven by a dual-functional small molecule (DFSM). By combining different P450BM3 variants with DFSMs, more than half of all possible hydroxylated products were obtained from each substrate with high regioselectivity (>99%), enantioselectivity (>99% ee), and high total turnover numbers (up to 80963). Synergistic effects between exogenous DFSMs and the protein environment controlled the regio- and enantioselectivity, as revealed by crystal structure analysis, molecular dynamic simulations, and theoretical calculations. This work has implications for exogenous-molecule-modulated enzymatic regiodivergent and enantioselective hydroxylation with potential applications in synthetic chemistry.

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION (2023)

Article Chemistry, Multidisciplinary

Engineering Cytochrome P450BM3 Enzymes for Direct Nitration of Unsaturated Hydrocarbons

Xiling Wang, Xiaodan Lin, Yiping Jiang, Xiangquan Qin, Nana Ma, Fuquan Yao, Sheng Dong, Chuanfei Liu, Yingang Feng, Longyi Jin, Mo Xian, Zhiqi Cong

Summary: The peroxidase activity of cytochrome P450BM3 was increased through protein engineering by introducing site-directed mutations of key active-site residues. This allowed for efficient regulation of substrate access, leading to a decrease in monooxygenation activity and an increase in peroxidase activity. The P450 peroxidase system was successfully applied for the direct nitration of aromatic compounds and terminal aryl-substituted olefins.

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION (2023)

Article Biochemistry & Molecular Biology

Crystal Structure of the SH3 Domain of ASAP1 in Complex with the Proline Rich Motif (PRM) of MICAL1 Reveals a Unique SH3/PRM Interaction Mode

Xuanyan Jia, Leishu Lin, Shun Xu, Lingxuan Li, Zhiyi Wei, Cong Yu, Fengfeng Niu

Summary: This study identified a specific binding interaction between the SH3 domain of ASAP1 and the PRM domain of MICAL1, and revealed the unique structure of the target-binding pocket in ASAP1-SH3. This unique structure was also found in the SH3 domains of GRAF and SKAP1. Furthermore, over 130 proteins with the SH3(AGS)-binding PRM were found in the protein database. Gene ontology analysis suggests that the strong interaction between SH3(AGS)-containing proteins and their targets may play roles in actin cytoskeleton regulation and vesicle trafficking.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2023)

Review Biochemistry & Molecular Biology

Hydrogenase and Nitrogenase: Key Catalysts in Biohydrogen Production

Jinsong Xuan, Lingling He, Wen Wen, Yingang Feng

Summary: Biohydrogen production through microbes offers a renewable and abundant hydrogen supply by utilizing raw materials like sunlight, water, and organic waste, thus addressing the issues of energy supply and environmental protection simultaneously.

MOLECULES (2023)

Review Chemistry, Physical

Recent Progress in the Mechanism and Engineering of α/β Hydrolases for Chiral Chemical Production

Mingzhe Qiu, Sheng Dong, Qiu Cui, Yingang Feng, Jinsong Xuan

Summary: Chiral compounds play an important role in the chemical and pharmaceutical industry, and the production of high enantiopurity chemicals is a major goal in asymmetric catalysis. Enzymatic synthesis, particularly using alpha/beta hydrolases, offers a sustainable and environmentally friendly approach to produce chiral molecules. This review highlights the current understanding of the structures and reaction mechanisms of alpha/beta hydrolases, as well as the efforts in screening and protein engineering to develop biocatalysts for chiral chemicals production. Other strategies, such as whole-cell catalysis and protein immobilization, are also discussed to enhance the performance of alpha/beta hydrolases. The progress in biocatalyst development based on alpha/beta hydrolases will contribute to the green and sustainable development of the chemical and pharmaceutical industry.

CATALYSTS (2023)

Article Multidisciplinary Sciences

Autoinhibition and activation mechanisms revealed by the triangular-shaped structure of myosin Va

Fengfeng Niu, Yong Liu, Kang Sun, Shun Xu, Jiayuan Dong, Cong Yu, Kaige Yan, Zhiyi Wei

Summary: The study provides insights into the structural and functional regulation of myosin Va, revealing the molecular mechanisms of autoinhibition and activation as well as the specific activation mechanism dependent on multiple cargo adaptors.

SCIENCE ADVANCES (2022)

Article Chemistry, Applied

Structural characterization on a β-agarase Aga86A_Wa from Wenyingzhuangia aestuarii reveals the prevalent methyl-galactose accommodation capacity of GH86 enzymes at subsite-1

Yuying Zhang, Sheng Dong, Guangning Chen, Siqi Cao, Jingjing Shen, Xuanwei Mei, Qiu Cui, Yingang Feng, Yaoguang Chang, Yanchao Wang, Changhu Xue

Summary: In this study, the structure of GH86 beta-agarase Aga86A_Wa was determined and its methyl-galactose tolerance was investigated. It was found that an accommodation pocket at subsite -1 contributed to the tolerance of methyl-galactose. Similar pockets were also found in two other GH86 enzymes, BuGH86 and BpGH86A, confirming their function in methyl-galactose accommodation. These findings provide insights into the function and mechanism of GH86 agaran degrading enzymes and have implications for the precise preparation of agaran oligosaccharides.

CARBOHYDRATE POLYMERS (2023)

Review Biotechnology & Applied Microbiology

Glycoside Hydrolase Family 48 Cellulase: A Key Player in Cellulolytic Bacteria for Lignocellulose Biorefinery

Cai You, Ya-Jun Liu, Qiu Cui, Yingang Feng

Summary: GH48 cellulases are widely distributed in cellulolytic microorganisms, especially in the highly efficient cellulose-degrading ruminal system. They hydrolyze cellulose using an inverting mechanism in a processive mode. In addition, GH48 cellulases greatly synergize with endoglucanases to improve cellulose hydrolysis efficiency.

FERMENTATION-BASEL (2023)

Article Biology

Structural insights into MIC2 recognition by MIC2-associated protein in Toxoplasma gondii

Su Zhang, Fangfang Wang, Dujuan Zhang, Dongsheng Liu, Wei Ding, Timothy A. Springer, Gaojie Song

Summary: Microneme protein 2 (MIC2) and MIC2-associated protein (M2AP) are essential for the gliding motility and invasion of Toxoplasma gondii. This study reveals the crystal structures of M2AP and its complex with a TSR domain of MIC2 (TSR6). The findings provide insights into the formation and stability of the MIC2-M2AP complex and have implications for developing new therapies against this parasite.

COMMUNICATIONS BIOLOGY (2023)

Article Endocrinology & Metabolism

Functional screening and rational design of compounds targeting GPR132 to treat diabetes

Jia-Le Wang, Xiao-Dong Dou, Jie Cheng, Ming-Xin Gao, Guo-Feng Xu, Wei Ding, Jin-Hui Ding, Yu Li, Si-Han Wang, Zhao-Wei Ji, Xin-Yi Zhao, Tong-Yu Huo, Cai-Fang Zhang, Ya-Meng Liu, Xue-Ying Sha, Jia-Rui Gao, Wen-Hui Zhang, Yong Hao, Cheng Zhang, Jin-Peng Sun, Ning Jiao, Xiao Yu

Summary: This study systematically analyzed the lipid-transmembrane receptor signaling in islet-resident macrophages and identified GPR132-Gi signaling as an important contributor to islet macrophage reprogramming. The researchers successfully designed selective GPR132 antagonists, which could potentially be used for treating refractory diseases such as diabetes.

NATURE METABOLISM (2023)

暂无数据