| 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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| 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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