| Project/Area Number |
26460037
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Physical pharmacy
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| Research Institution | Kumamoto University |
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Principal Investigator |
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| Co-Investigator(Renkei-kenkyūsha) |
WACHINO Jun-ichi 名古屋大学, 大学院医学系研究科, 講師 (00535651)
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| Research Collaborator |
KIRIKAE Teruo
FUJITA Mikako
SHIMIZU Nobutaka
YAMAGATA Yuriko
KUROSAKI Hiromasa
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2014: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
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| Keywords | 加水分解酵素 / 薬剤耐性菌 / メタロ-β-ラクタマーゼ / Zn(II)イオン / 結晶構造 / 溶液構造 / 速度論的解析 / メタロ－β－ラクタマーゼ / 高触媒活性 / β-ラクタム剤 / 加水分解機構 / 亜鉛酵素 / 基質認識 / 触媒機構 / Zn酵素 / X線小角散乱 |
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| Outline of Final Research Achievements |
The enzyme KHM-1 is a metallo-β-lactamase (MBL) that hydrolyzes almost all β-lactam antibiotics; compared with other MBLs, KHM-1 has a higher catalytic efficiency for hydrolyzing cephem antibiotics. The objective of this study was to elucidate the mechanism underlying the high catalytic efficiency of KHM-1. Analysis of the crystal structure of KHM-1 showed that one of the two Zn(II) ions in the active site easily dissociates. Small-angle X-ray scattering analysis revealed that the particle size of KHM-1 in solution is small than that of other MBLs (e.g., IMP-1, with a structure similar to that of KHM-1). Kinetic analysis of KHM-1 revealed that His170 of KHM-1, which is located near the active site, plays an important role in the enzyme’s hydrolytic activity
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