抄録
A mechanism of the C-S bond activation of S-adenosylmethionine (SAM) in biotin synthase is discussed from quantum mechanical/molecular mechanical (QM/MM) computations. The active site of the enzyme involves a [4Fe-4S] cluster, which is coordinated to the COO- and NH2 groups of the methionine moiety of SAM. The unpaired electrons on the iron atoms of the [4Fe-4S]2+ cluster are antiferromagnetically coupled, resulting in the S = 0 ground spin state. An electron is transferred from an electron donor to the [4Fe-4S]2+-SAM complex to produce the catalytically active [4Fe-4S]+ state. The SOMO of the [4Fe-4S]+-SAM complex is localized on the [4Fe-4S] moiety and the spin density of the [4Fe-4S] core is calculated to be 0.83. The C-S bond cleavage is associated with the electron transfer from the [4Fe-4S]+ cluster to the antibonding σ* C-S orbital. The electron donor and acceptor states are effectively coupled with each other at the transition state for the C-S bond cleavage. The activation barrier is calculated to be 16.0 kcal/mol at the QM (B3LYP/SV(P))/MM (CHARMm) level of theory and the C-S bond activation process is 17.4 kcal/mol exothermic, which is in good agreement with the experimental observation that the C-S bond is irreversibly cleaved in biotin synthase. The sulfur atom of the produced methionine molecule is unlikely to bind to an iron atom of the [4Fe-4S]2+ cluster after the C-S bond cleavage from the energetical and structural points of view.
| 元の言語 | 英語 |
|---|---|
| ページ（範囲） | 850-857 |
| ページ数 | 8 |
| ジャーナル | Journal of Inorganic Biochemistry |
| 巻 | 105 |
| 発行部数 | 6 |
| DOI | |
| 出版物ステータス | 出版済み - 6 1 2011 |
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All Science Journal Classification (ASJC) codes
- Biochemistry
- Inorganic Chemistry
これを引用
Generation of adenosyl radical from S-adenosylmethionine (SAM) in biotin synthase. / Kamachi, Takashi; Kouno, Tomohisa; Doitomi, Kazuki; Yoshizawa, Kazunari.
：: Journal of Inorganic Biochemistry, 巻 105, 番号 6, 01.06.2011, p. 850-857.研究成果: ジャーナルへの寄稿 › 記事
}
TY - JOUR
T1 - Generation of adenosyl radical from S-adenosylmethionine (SAM) in biotin synthase
AU - Kamachi, Takashi
AU - Kouno, Tomohisa
AU - Doitomi, Kazuki
AU - Yoshizawa, Kazunari
PY - 2011/6/1
Y1 - 2011/6/1
N2 - A mechanism of the C-S bond activation of S-adenosylmethionine (SAM) in biotin synthase is discussed from quantum mechanical/molecular mechanical (QM/MM) computations. The active site of the enzyme involves a [4Fe-4S] cluster, which is coordinated to the COO- and NH2 groups of the methionine moiety of SAM. The unpaired electrons on the iron atoms of the [4Fe-4S]2+ cluster are antiferromagnetically coupled, resulting in the S = 0 ground spin state. An electron is transferred from an electron donor to the [4Fe-4S]2+-SAM complex to produce the catalytically active [4Fe-4S]+ state. The SOMO of the [4Fe-4S]+-SAM complex is localized on the [4Fe-4S] moiety and the spin density of the [4Fe-4S] core is calculated to be 0.83. The C-S bond cleavage is associated with the electron transfer from the [4Fe-4S]+ cluster to the antibonding σ* C-S orbital. The electron donor and acceptor states are effectively coupled with each other at the transition state for the C-S bond cleavage. The activation barrier is calculated to be 16.0 kcal/mol at the QM (B3LYP/SV(P))/MM (CHARMm) level of theory and the C-S bond activation process is 17.4 kcal/mol exothermic, which is in good agreement with the experimental observation that the C-S bond is irreversibly cleaved in biotin synthase. The sulfur atom of the produced methionine molecule is unlikely to bind to an iron atom of the [4Fe-4S]2+ cluster after the C-S bond cleavage from the energetical and structural points of view.
AB - A mechanism of the C-S bond activation of S-adenosylmethionine (SAM) in biotin synthase is discussed from quantum mechanical/molecular mechanical (QM/MM) computations. The active site of the enzyme involves a [4Fe-4S] cluster, which is coordinated to the COO- and NH2 groups of the methionine moiety of SAM. The unpaired electrons on the iron atoms of the [4Fe-4S]2+ cluster are antiferromagnetically coupled, resulting in the S = 0 ground spin state. An electron is transferred from an electron donor to the [4Fe-4S]2+-SAM complex to produce the catalytically active [4Fe-4S]+ state. The SOMO of the [4Fe-4S]+-SAM complex is localized on the [4Fe-4S] moiety and the spin density of the [4Fe-4S] core is calculated to be 0.83. The C-S bond cleavage is associated with the electron transfer from the [4Fe-4S]+ cluster to the antibonding σ* C-S orbital. The electron donor and acceptor states are effectively coupled with each other at the transition state for the C-S bond cleavage. The activation barrier is calculated to be 16.0 kcal/mol at the QM (B3LYP/SV(P))/MM (CHARMm) level of theory and the C-S bond activation process is 17.4 kcal/mol exothermic, which is in good agreement with the experimental observation that the C-S bond is irreversibly cleaved in biotin synthase. The sulfur atom of the produced methionine molecule is unlikely to bind to an iron atom of the [4Fe-4S]2+ cluster after the C-S bond cleavage from the energetical and structural points of view.
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UR - http://www.scopus.com/inward/citedby.url?scp=79955083639&partnerID=8YFLogxK
U2 - 10.1016/j.jinorgbio.2011.03.013
DO - 10.1016/j.jinorgbio.2011.03.013
M3 - Article
VL - 105
SP - 850
EP - 857
JO - Journal of Inorganic Biochemistry
JF - Journal of Inorganic Biochemistry
SN - 0162-0134
IS - 6
ER -