| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Outline of Final Research Achievements |
An alternative biosynthetic pathway of menaquinone (vitamin K2) was found in some microorganisms including Streptomyces coelicolor and Thermus thermophilus. Since the pathogenic species such as Helicobacter pylori and Campylobacter jejuni also have essential enzymes in the alternative menaquinone biosynthetic pathway, the enzymes are attractive targets for the development of chemotherapeutics. Here we report the 1.5 angstrom crystal structure of the H145A variant of MqnD from T. thermophiles, complexed with its substrate. The substrate with ring-closing form was bound to the active-site pocket between the two domains, a large domain and a small domain. The His145Ala variant produces no enzymatic reaction, suggesting that His145 is an essential active residue as a catalytic base. Furthermore, we solved the crystal structure of MqnD complexed with the product, one of its reaction products. These results provide new insights into the enzymatic reaction mechanism of MqnD.
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