Analysis of enlargement mechanism of substrate specificity of CTX-M type beta-lactamase based on protein crystallography.
| Project/Area Number |
25670276
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Laboratory medicine
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| Research Institution | Nara Medical University |
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Principal Investigator |
YAMAMOTO Keizo 奈良県立医科大学, 医学部, 准教授 (90254490)
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| Co-Investigator(Kenkyū-buntansha) |
KASAHARA Kei 奈良県立医科大学, 医学部, 准教授 (50405403)
NAKAYAMA Akifumi 岐阜医療科学大学, 保険科学部, 教授 (70536721)
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | βーラクタマーゼ / X線結晶構造解析 / 基質特異性 / 構造変化 / β―ラクタマーゼ / Ｘ線結晶構造解析 / 多剤耐性 / タンパク質精製 / クローニング / 大量発現 / 大腸菌 |
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| Outline of Final Research Achievements |
Plasmid-mediated extended spectrum beta-lactamases (ESBLs) named CTX-M causes hospital- and community-acquired infections in Japan. Comparison of DNA sequences and structures of CTX-Ms showed that amino acid substitution in the three loop regions, omega-loop, VNYNP-loop, and a loop connecting alpha/beta domain mast be important to change of substrate specificity. Ala-219 which locates in a loop connecting alpha/beta domain is considered as a key residue to substrate specificity. Thus, the structures of three mutant enzymes, A219V, A219L, A219F, and wild type CTX-M-2 were solved. Although the structural difference among wild type, A219V, and A219F were very small, maximum XYZ-difference between wild type and A219L were 0.42 nm. It reveals that the structure of CTX-Ms is latently flexible and mutation in the loop region raises changes of overall structure and substrate specificity.
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Report
(4 results)
Research Products
(22 results)
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[Journal Article] Chronic invasive sinus and intracerebral aspergillosis controlled by combination therapy with micafungin and a daily dose of 400 mg itraconazole oral solution.2015
Author(s)
Ogawa T, Matsumoto K, Tsujimoto K, Hishiya N, Yamada Y, Uno K, Kasahara K, Maeda K, Nario K, Mikasa K, Morita K.
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Journal Title
J． Infect． Chemother.
Volume: 21
Issue: 2
Pages: 134-137
DOI
Related Report
Peer Reviewed
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