دورية أكاديمية
Structural basis for substrate recognition by a S-adenosylhomocysteine hydrolase Lpg2021 from Legionella pneumophila.
| العنوان: | Structural basis for substrate recognition by a S-adenosylhomocysteine hydrolase Lpg2021 from Legionella pneumophila. |
|---|---|
| المؤلفون: | Gao Y; Institute of Health Sciences and Technology, Institutes of Material Science and Information Technology, Anhui University, Hefei 230601, China; School of Resources and Environmental Engineering, Anhui University, Hefei 230601, China., Xie R; Institute of Health Sciences and Technology, Institutes of Material Science and Information Technology, Anhui University, Hefei 230601, China., Chen Y; Institute of Health Sciences and Technology, Institutes of Material Science and Information Technology, Anhui University, Hefei 230601, China., Yang B; Institute of Health Sciences and Technology, Institutes of Material Science and Information Technology, Anhui University, Hefei 230601, China., Wang M; Institute of Health Sciences and Technology, Institutes of Material Science and Information Technology, Anhui University, Hefei 230601, China., Hua L; Institute of Health Sciences and Technology, Institutes of Material Science and Information Technology, Anhui University, Hefei 230601, China., Wang X; Institute of Health Sciences and Technology, Institutes of Material Science and Information Technology, Anhui University, Hefei 230601, China., Wang W; Institute of Health Sciences and Technology, Institutes of Material Science and Information Technology, Anhui University, Hefei 230601, China., Wang N; Institute of Health Sciences and Technology, Institutes of Material Science and Information Technology, Anhui University, Hefei 230601, China. Electronic address: wangn6@ahu.edu.cn., Ge H; Institute of Health Sciences and Technology, Institutes of Material Science and Information Technology, Anhui University, Hefei 230601, China. Electronic address: hhge@ahu.edu.cn., Ma J; Institute of Health Sciences and Technology, Institutes of Material Science and Information Technology, Anhui University, Hefei 230601, China. Electronic address: jmma@ahu.edu.cn. |
| المصدر: | International journal of biological macromolecules [Int J Biol Macromol] 2024 Jun; Vol. 270 (Pt 1), pp. 132289. Date of Electronic Publication: 2024 May 10. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Country of Publication: Netherlands NLM ID: 7909578 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-0003 (Electronic) Linking ISSN: 01418130 NLM ISO Abbreviation: Int J Biol Macromol Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Amsterdam : Elsevier Original Publication: Guildford, Eng., IPC Science and Technology Press. |
| مواضيع طبية MeSH: | Legionella pneumophila*/enzymology , Molecular Docking Simulation* , Adenosylhomocysteinase*/metabolism , Adenosylhomocysteinase*/antagonists & inhibitors , Adenosylhomocysteinase*/chemistry, Substrate Specificity ; Crystallography, X-Ray ; Adenosine/analogs & derivatives ; Adenosine/metabolism ; Adenosine/chemistry ; Adenine/chemistry ; Adenine/metabolism ; Adenine/analogs & derivatives ; Protein Binding ; Bacterial Proteins/chemistry ; Bacterial Proteins/metabolism ; Enzyme Inhibitors/pharmacology ; Enzyme Inhibitors/chemistry ; N-Glycosyl Hydrolases |
| مستخلص: | S-Adenosyl-l-homocysteine hydrolase (SAHH) is a crucial enzyme that governs S-adenosyl methionine (SAM)-dependent methylation reactions within cells and regulates the intracellular concentration of SAH. Legionella pneumophila, the causative pathogen of Legionnaires' disease, encodes Lpg2021, which is the first identified dimeric SAHH in bacteria and is a promising target for drug development. Here, we report the structure of Lpg2021 in its ligand-free state and in complexes with adenine (ADE), adenosine (ADO), and 3-Deazaneplanocin A (DZNep). X-ray crystallography, isothermal titration calorimetry (ITC), and molecular docking were used to elucidate the binding mechanisms of Lpg2021 to its substrates and inhibitors. Virtual screening was performed to identify potential Lpg2021 inhibitors. This study contributes a novel perspective to the understanding of SAHH evolution and establishes a structural framework for designing specific inhibitors targeting pathogenic Legionella pneumophila SAHH. Competing Interests: Declaration of competing interest We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, there is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the position presented in, or the review of, the manuscript entitled. (Copyright © 2024 Elsevier B.V. All rights reserved.) |
| فهرسة مساهمة: | Keywords: Crystal structure; Inhibitors; SAH hydrolase |
| المشرفين على المادة: | EC 3.3.1.1 (Adenosylhomocysteinase) K72T3FS567 (Adenosine) JAC85A2161 (Adenine) 0 (Bacterial Proteins) EC 3.2.2.9 (adenosylhomocysteine nucleosidase) 0 (Enzyme Inhibitors) EC 3.2.2.- (N-Glycosyl Hydrolases) |
| تواريخ الأحداث: | Date Created: 20240512 Date Completed: 20240604 Latest Revision: 20240604 |
| رمز التحديث: | 20240604 |
| DOI: | 10.1016/j.ijbiomac.2024.132289 |
| PMID: | 38735607 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1879-0003 |
|---|---|
| DOI: | 10.1016/j.ijbiomac.2024.132289 |