Structure-based discovery of metallo-type carbapenemase inhibitor and application to bacteriological examination
| Project/Area Number |
24790570
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Laboratory medicine
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| Research Institution | Nagoya University |
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Principal Investigator |
WACHINO Jun-ichi 名古屋大学, 医学(系)研究科(研究院), 助教 (00535651)
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2014: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2013: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | 薬剤耐性菌 / メタロβ-ラクタマーゼ / カルバペネム耐性 / メタロ-β-ラクタマーゼ / SMB-1 / D-captopril / 薬剤耐性 |
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| Outline of Final Research Achievements |
We determined the crystal structure of SMB-1 using 1.6A diffraction data, and revealed that the overall structure of SMB-1 was quite similar to those of the other subclass B3 MBLs, AIM-1, L1, and BJP-1. The electron density map corresponding to a water molecule (wat1), which is assumed to contribute as the attacking nucleophile on the carbonyl carbon of the beta-lactam ring, was observed. SMB-1 possesses a unique amino acid residue, Q157, which probably plays a role in recognition of beta-lactams via the hydrogen bond interaction. In addition, we determined the mercaptoacetate (MCR)-complexed SMB-1 structure and revealed that the mode of its inhibition by MCR: the thiolate group bridges to two zinc ions (Zn1 and Zn2), and occupy the space to which beta-lactams originally bind. Finally, we performed in silico screening to find effective inhibitors of SMB-1 and found four agents which could behave as inhibitors of SMB-1.
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Report
(4 results)
Research Products
(19 results)
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[Journal Article] Invasive infection caused by carbapenem-resistant Acinetobacter soli, Japan.2014
Author(s)
Kitanaka H, Sasano MA, Yokoyama S, Suzuki M, Jin W, Inayoshi M, Hori M, Wachino J, Kimura K, Yamada K, Arakawa Y.
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Journal Title
Emerg Infect Dis
Volume: 20
Issue: 9
Pages: 1574-6
DOI
Related Report
Peer Reviewed
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