Characterization of the proteins involved in iron uptake system of pathogen and its application to development of anti-bacterial drugs

2014 Fiscal Year Final Research Report

• Project/Area Number: 24550182
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Chemistry related to living body
• Research Institution: Hokkaido University
• Principal Investigator: UCHIDA Takeshi 北海道大学, 理学(系)研究科(研究院), 准教授 (30343742)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 病原菌 / 鉄 / 酵素 / ヘム

Outline of Final Research Achievements

Iron is an essential element for bacteria survival. To obtain this element, bacterial pathogens utilize heme from hemoglobin in blood as an iron source, because the vast majority of iron in human body is present as heme. In this project, we found that VCA0907 (HutZ) from Vibrio cholerae is a heme-degrading enzyme. The activity of VCA0907 depends on the strength of the hydrogen bond between His170 that is a sole ligand of heme, and Asp132. We further found that VCA0908 (HutX) binds to heme with a slightly higher affinity than that of HutZ. Unexpectedly, heme, which is bound to HutX, irreversibly moves to HutZ. We concluded that heme that is transported into cytosol is captured by HutX, and then it is transferred to HutZ through the direct interaction with HutX. Finally, HutZ degrades heme to release iron, which is used for survival of V. cholerae. Because iron is an essential element, our findings lead to development of a new kind of medicine for pathogens.

Free Research Field

生物無機化学