S-Adenosylhomocysteine hydrolase (AdoHcyase)
1. S-Adenosylhomocysteine hydrolase (AdoHcyase) catalyzes the hydrolysis reaction of SAH to Ado and Hcy
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2. Crystal structures of AdoHcyase complexed with various inhibitors were determined.
Tetrameric AdoHcyase with SAH and Ado
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3. AdoHcyase has at least two conformations. The enzyme changes the conformation upon the substrate/inhibitor binding.
Open conformation
Closed conformation
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Dynamic motion of individual subunit
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4. Catalytic mechanism based on the crystal structures, site-directed mechanisms, and etc.
(A) (B)
(C) (D)
(E)
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Publications:
● Hu, Y, Komoto, J., Huang, Y., Gomi, T., Ogawa, H.,
Takata, Y., Fujioka, M. & Takusagawa, F. (1999). “Crystal Structure of S-Adenosylhomocysteine
Hydrolase from Rat Liver" Biochemistry
38, 8323-8333.
● Komoto, J.,
Huang, Y., Gomi, T., Ogawa, H., Takata, Y., Fujioka, M. & Takusagawa, F.
(2000). Effects of Site-Directed Mutagenesis on the Structure of S-Adenosylhomocysteine Hydrolase:
Crystal Structure of D244E Mutant Enzyme.
J. Biol. Chem. 275, 32147-32156.
● Huang, Y.,
Komoto, J., Takata, Y., Powell, D. R., Gomi, T., Ogawa, H., Fujioka, M. & Takusagawa,
F. (2002). Inhibition of S-Adenosylhomocysteine Hydrolase by
"Acyclic Sugar" Adenosine Analogue D-Eritadenine: Crystal Structure
of S-Adenosylhomocysteine Hydrolase Complexed with D-Eritadenine. J. Biol. Chem. 277, 7477-7482.
● Takata, Y., Yamada, T., Huang, Y., Komoto, J., Gomi, T., Ogawa, H., Fujioka, M. & Takusagawa, F. (2002). Catalytic Mechanism of S-Adenosylhomocysteine Hydrolase: Site-directed Mutagenesis of Asp-130, Lys-185, Asp-189, and Asn-190. J. Biol. Chem. 277, 22670-22676.