Analysis of unknown activity of metallo-beta-lactamase and search for novel inhibitors

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K07566
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49050:Bacteriology-related
• Research Institution: Nigata University of Phermacy and Applied Life Sciences
• Principal Investigator: Ibuka Akiko 新潟薬科大学, 応用生命科学部, 教授 (60301420)
• Co-Investigator(Kenkyū-buntansha): 梨本 正之 新潟薬科大学, 健康・自立総合研究機構, 教授 (30228069)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: MBLスーパーファミリー / β-ラクタマーゼ / ホモセリンラクトナーゼ

Outline of Final Research Achievements

Many beta-lactam drug-resistant bacteria acquire resistance through the production of the enzyme beta-lactamase. Metallo-beta-lactamases (MBLs) have degrading activity against a wide range of beta-lactam drugs, and there are no clinically available inhibitors. We analyzed the MBL enzymes IMP-1 and IMP-27 in the presence of chelating agents and found that IMP-27, which is derived from IMP-1, acquired zinc deficiency tolerance. We also analyzed the catalytic activity of IMP-1 toward the substrates of MBL-like enzymes, whose steric structure is similar to that of MBL. The results revealed that IMP-1 has RNase activity. The inhibition of beta-lactamase activity by substrates of MBL-like enzymes has not been confirmed at this time.

Free Research Field

構造生物学、酵素学

Academic Significance and Societal Importance of the Research Achievements

β-ラクタム剤は感染症治療に多用される抗生物質である。感染症の原因菌は、この薬剤を分解する酵素β-ラクタマーゼを生産する。これらの酵素は、新規薬剤の使用に伴い変化（分子進化）すると考えられている。我々はβ-ラクタマーゼIMP-1、IMP-27し、IMP-1から派生したIMP-27が亜鉛欠乏耐性を獲得していることを明らかにした。さらに、IMP-1が本来の活性以外に核酸分解活性を有することを示した。