抄録
Detailed theoretical and X-ray based structural analysis has been carried out in order to unmask the role of the tyrosine residue (Y) in the activation of the Co-C bond in AdoCbl-dependent mutases. In particular, methylmalonyl-CoA mutase (MCM) and glutamate mutase (GLM) enzymes have been studied; in the case of MCM, the significance of the Y89 residue has been analyzed extensively. Three different theoretical platforms encompassing the DFT, CASSCF/QDPT2, and QM/MM frameworks have been employed to elucidate the energetics of the AdoCbl-Y - complex while taking into account a varied degree of structural complexity. The diradical state, [AdoCbl]•--Y•, has been found to be the lowest electronic state of the AdoCbl-Y- complex, providing strong evidence that electron transfer from the Y89 residue to the cofactor is feasible. Crystallographic analysis of the active sites of MCM and GLM enzymes reveals that substrate binding can play a critical role in displacing the hydroxyl proton of the Y residue (Y89 in the case of MCM enzyme and Y181 in the case of GLM enzyme) that will facilitate the electron transfer (ET), hence making the activation process a case of proton-coupled electron transfer (PCET). PCET-inspired enzymatic catalysis implies that the cleavage of the Co-C bond takes place via one-electron reduced form of the AdoCbl cofactor (i.e., [AdoCbl]•-), rather than its neutral analogue, thus providing an efficient mode of cleavage that can help in understanding the origin of the catalytic effect in such enzymes.
| 元の言語 | 英語 |
|---|---|
| ページ（範囲） | 5928-5939 |
| ページ数 | 12 |
| ジャーナル | Journal of Physical Chemistry B |
| 巻 | 114 |
| 発行部数 | 17 |
| DOI | |
| 出版物ステータス | 出版済み - 5 6 2010 |
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All Science Journal Classification (ASJC) codes
- Physical and Theoretical Chemistry
- Surfaces, Coatings and Films
- Materials Chemistry
これを引用
Theoretical analysis of the diradical nature of adenosylcobalamin cofactor-tyrosine complex in B12-dependent mutases : Inspiring PCET-driven enzymatic catalysis. / Kozlowski, Pawel M.; Kamachi, Takashi; Kumar, Manoj; Nakayama, Tomonori; Yoshizawa, Kazunari.
：: Journal of Physical Chemistry B, 巻 114, 番号 17, 06.05.2010, p. 5928-5939.研究成果: ジャーナルへの寄稿 › 記事
}
TY - JOUR
T1 - Theoretical analysis of the diradical nature of adenosylcobalamin cofactor-tyrosine complex in B12-dependent mutases
T2 - Inspiring PCET-driven enzymatic catalysis
AU - Kozlowski, Pawel M.
AU - Kamachi, Takashi
AU - Kumar, Manoj
AU - Nakayama, Tomonori
AU - Yoshizawa, Kazunari
PY - 2010/5/6
Y1 - 2010/5/6
N2 - Detailed theoretical and X-ray based structural analysis has been carried out in order to unmask the role of the tyrosine residue (Y) in the activation of the Co-C bond in AdoCbl-dependent mutases. In particular, methylmalonyl-CoA mutase (MCM) and glutamate mutase (GLM) enzymes have been studied; in the case of MCM, the significance of the Y89 residue has been analyzed extensively. Three different theoretical platforms encompassing the DFT, CASSCF/QDPT2, and QM/MM frameworks have been employed to elucidate the energetics of the AdoCbl-Y - complex while taking into account a varied degree of structural complexity. The diradical state, [AdoCbl]•--Y•, has been found to be the lowest electronic state of the AdoCbl-Y- complex, providing strong evidence that electron transfer from the Y89 residue to the cofactor is feasible. Crystallographic analysis of the active sites of MCM and GLM enzymes reveals that substrate binding can play a critical role in displacing the hydroxyl proton of the Y residue (Y89 in the case of MCM enzyme and Y181 in the case of GLM enzyme) that will facilitate the electron transfer (ET), hence making the activation process a case of proton-coupled electron transfer (PCET). PCET-inspired enzymatic catalysis implies that the cleavage of the Co-C bond takes place via one-electron reduced form of the AdoCbl cofactor (i.e., [AdoCbl]•-), rather than its neutral analogue, thus providing an efficient mode of cleavage that can help in understanding the origin of the catalytic effect in such enzymes.
AB - Detailed theoretical and X-ray based structural analysis has been carried out in order to unmask the role of the tyrosine residue (Y) in the activation of the Co-C bond in AdoCbl-dependent mutases. In particular, methylmalonyl-CoA mutase (MCM) and glutamate mutase (GLM) enzymes have been studied; in the case of MCM, the significance of the Y89 residue has been analyzed extensively. Three different theoretical platforms encompassing the DFT, CASSCF/QDPT2, and QM/MM frameworks have been employed to elucidate the energetics of the AdoCbl-Y - complex while taking into account a varied degree of structural complexity. The diradical state, [AdoCbl]•--Y•, has been found to be the lowest electronic state of the AdoCbl-Y- complex, providing strong evidence that electron transfer from the Y89 residue to the cofactor is feasible. Crystallographic analysis of the active sites of MCM and GLM enzymes reveals that substrate binding can play a critical role in displacing the hydroxyl proton of the Y residue (Y89 in the case of MCM enzyme and Y181 in the case of GLM enzyme) that will facilitate the electron transfer (ET), hence making the activation process a case of proton-coupled electron transfer (PCET). PCET-inspired enzymatic catalysis implies that the cleavage of the Co-C bond takes place via one-electron reduced form of the AdoCbl cofactor (i.e., [AdoCbl]•-), rather than its neutral analogue, thus providing an efficient mode of cleavage that can help in understanding the origin of the catalytic effect in such enzymes.
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U2 - 10.1021/jp100573b
DO - 10.1021/jp100573b
M3 - Article
VL - 114
SP - 5928
EP - 5939
JO - Journal of Physical Chemistry B
JF - Journal of Physical Chemistry B
SN - 1520-6106
IS - 17
ER -