| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Outline of Final Research Achievements |
Iron is an essential element for bacterial growth because it is contained in proteins playing key roles in metabolic processes. Most irons in the human body are present as a heme iron. Therefore, heme is a dominant iron source for most pathogens. In this project the reaction mechanism of a heme-degrading enzyme HutZ from V. cholerae was solved. We found that iron chelators are able to inhibit HutZ by perturbing the proton transfer to heme intermediate. This mechanism suggests that iron chelators are candidates of antibiotics. We further found that heme binds to iron-carrier protein CyaY and PBGD that catalyzes the polymerization of porphobilinogen to form 1-hydroxymethylbilane. Heme binding to CyaY and PBGD resulted in less activity, indicating the presence of heme-induced negative feedback. These were not observed in the corresponding human proteins. Therefore, we can propose that HutZ, CyaY and PBGD are good target for new medicine to repress pathogen growth without side reaction.
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