| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2017: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Outline of Final Research Achievements |
We have processed the X-ray diffraction data and determined the crystal structure of human histidine decarboxylase (HDC) in complex with a novel inhibitor, aminooxy analog of histamine. By comparing it with the HDC complex with histidine methyl ester, we confirmed that the tyrosine (Y334) existing on the catalytic loop plays an important role in decarboxylation reaction. The Y334F mutant were crystallized under the same crystallization conditions used for wild type HDC-inhibitor complex. By soaking the substrate histidine into the crystal of Y334F mutant, the structure of the reaction intermediate has been determined. Furthermore, by comparing with the structures of vitamin B6 dependent enzymes, we suggest that the corresponding tyrosine residue of all decarboxylases has a common catalytic function.
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