دورية أكاديمية
أعرض في EDS

Nontraditional Roles of Magnesium Ions in Modulating Sav2152: Insight from a Haloacid Dehalogenase-like Superfamily Phosphatase from Staphylococcus aureus .

التفاصيل البيبلوغرافية
العنوان: Nontraditional Roles of Magnesium Ions in Modulating Sav2152: Insight from a Haloacid Dehalogenase-like Superfamily Phosphatase from Staphylococcus aureus .
المؤلفون: Bang J; College of Pharmacy, Chungbuk National University, Cheongju 28160, Republic of Korea., Park J; College of Pharmacy, Chungbuk National University, Cheongju 28160, Republic of Korea., Lee SH; College of Pharmacy, Chungbuk National University, Cheongju 28160, Republic of Korea., Jang J; College of Pharmacy, Chungbuk National University, Cheongju 28160, Republic of Korea., Hwang J; College of Pharmacy, Chungbuk National University, Cheongju 28160, Republic of Korea., Kamarov O; College of Pharmacy, Chungbuk National University, Cheongju 28160, Republic of Korea., Park HJ; College of Pharmacy, Chungbuk National University, Cheongju 28160, Republic of Korea., Lee SJ; College of Pharmacy, Chungbuk National University, Cheongju 28160, Republic of Korea., Seo MD; Department of Molecular Science and Technology, Ajou University, Suwon 16499, Republic of Korea.; College of Pharmacy, Research Institute of Pharmaceutical Science and Technology (RIPST), Ajou University, Suwon 16499, Republic of Korea., Won HS; Department of Biotechnology, Research Institute (RIBHS), College of Biomedical and Health Science, Konkuk University, Chungju 27478, Republic of Korea.; BK21 Project Team, Department of Applied Life Science, Graduate School, Konkuk University, Chungju 27478, Republic of Korea., Seok SH; College of Pharmacy, Interdisciplinary Graduate Program in Advanced Convergence Technology and Science, Jeju National University, Jeju 632433, Republic of Korea., Kim JH; College of Pharmacy, Chungbuk National University, Cheongju 28160, Republic of Korea.
المصدر: International journal of molecular sciences [Int J Mol Sci] 2024 May 04; Vol. 25 (9). Date of Electronic Publication: 2024 May 04.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Basel, Switzerland : MDPI, [2000-
مواضيع طبية MeSH: Magnesium*/metabolism , Bacterial Proteins*/metabolism , Bacterial Proteins*/chemistry , Bacterial Proteins*/genetics , Phosphoric Monoester Hydrolases*/metabolism , Phosphoric Monoester Hydrolases*/chemistry , Phosphoric Monoester Hydrolases*/genetics , Hydrolases*/metabolism , Hydrolases*/chemistry , Hydrolases*/genetics, Models, Molecular ; Methicillin-Resistant Staphylococcus aureus/enzymology ; Methicillin-Resistant Staphylococcus aureus/genetics ; Staphylococcus aureus/enzymology ; Crystallography, X-Ray ; Protein Binding
مستخلص: Methicillin-resistant Staphylococcus aureus (MRSA) infection has rapidly spread through various routes. A genomic analysis of clinical MRSA samples revealed an unknown protein, Sav2152, predicted to be a haloacid dehalogenase (HAD)-like hydrolase, making it a potential candidate for a novel drug target. In this study, we determined the crystal structure of Sav2152, which consists of a C2-type cap domain and a core domain. The core domain contains four motifs involved in phosphatase activity that depend on the presence of Mg 2+ ions. Specifically, residues D10, D12, and D233, which closely correspond to key residues in structurally homolog proteins, are responsible for binding to the metal ion and are known to play critical roles in phosphatase activity. Our findings indicate that the Mg 2+ ion known to stabilize local regions surrounding it, however, paradoxically, destabilizes the local region. Through mutant screening, we identified D10 and D12 as crucial residues for metal binding and maintaining structural stability via various uncharacterized intra-protein interactions, respectively. Substituting D10 with Ala effectively prevents the interaction with Mg 2+ ions. The mutation of D12 disrupts important structural associations mediated by D12, leading to a decrease in the stability of Sav2152 and an enhancement in binding affinity to Mg 2+ ions. Additionally, our study revealed that D237 can replace D12 and retain phosphatase activity. In summary, our work uncovers the novel role of metal ions in HAD-like phosphatase activity.
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معلومات مُعتمدة: NRF-2022R1A2C1010308 National Research Foundation of Korea; NRF-2017R1A5A2015541 National Research Foundation of Korea; 2021RIS-001 National Research Foundation of Korea; C330430 Korea Basic Science Institute
فهرسة مساهمة: Keywords: Staphylococcus aureus; crystal structure; function of magnesium ion; functional replacement; haloacid dehalogenase-like hydrolase; melting temperature; phosphatase
المشرفين على المادة: I38ZP9992A (Magnesium)
0 (Bacterial Proteins)
EC 3.1.3.2 (Phosphoric Monoester Hydrolases)
EC 3.- (Hydrolases)
EC 3.8.1.2 (2-haloacid dehalogenase)
تواريخ الأحداث: Date Created: 20240511 Date Completed: 20240511 Latest Revision: 20240513
رمز التحديث: 20240513
مُعرف محوري في PubMed: PMC11084212
DOI: 10.3390/ijms25095021
PMID: 38732240
قاعدة البيانات: MEDLINE
الوصف
تدمد:1422-0067
DOI:10.3390/ijms25095021