2016 Fiscal Year Final Research Report
Insights into Mobility and Stability of the OXA-58 Carbapenemase Structure with the N-zeta-Carboxylated Catalytic Residue Lysine.
| Project/Area Number |
15K21356
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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 |
Structural biochemistry
Bacteriology (including mycology)
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| Research Institution | Aoyama Gakuin University |
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Principal Investigator |
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| Project Period (FY) |
2015-04-01 – 2017-03-31
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| Keywords | 多剤耐性菌 / カルバペネム / ラクタマーゼ / 抗菌薬 / アシネトバクター / OXA-58 |
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| Outline of Final Research Achievements |
OXA-58 is a carbapenem-hydrolyzing class D β-lactamase (CHDL) from the multi-drug resistant Acinetobacter baumannii. The nitrogen atom (Nζ) of the catalytic residue Lys is spontaneously modified by Nζ-carboxylation in the presence of the carboxy donor NaHCO3. The increase of hydrolytic activity with the N-ζ-carboxylation (ζ-carbamic acid formation) has been well studied in class D β-lactamases, whereas its effect on protein stability has received little attention. We determined the crystal structure of OXA-58 in a novel crystal, and revealed the structure of the substrate-binding cleft in a closed state. The ζ-carbamic acid made hydrogen-bond network within the amino acid residues in the catalytic site. The ζ-carbamic acid was shown to increase not only OXA-58 hydrolytic activity but also OXA-58 stability through the formation of a hydrogen bond network connected to the Ω-loop structure, whereas the mobile loops accomodates the various β-lactams.
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| Free Research Field |
構造生物学
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