Abstract
The iron(II)- and 2-(oxo)glutarate-dependent (Fe/2OG) oxygenases catalyze an array of challenging transformations via a common iron(IV)-oxo (ferryl) intermediate, which in most cases abstracts hydrogen (H•) from an aliphatic carbon of the substrate. Although it has been shown that the relative disposition of the Fe-O and C-H bonds can control the rate of H• abstraction and fate of the resultant substrate radical, there remains a paucity of structural information on the actual ferryl states, owing to their high reactivity. We demonstrate here that the stable vanadyl ion [(VIV-oxo)2+] binds along with 2OG or its decarboxylation product, succinate, in the active site of two different Fe/2OG enzymes to faithfully mimic their transient ferryl states. Both ferryl and vanadyl complexes of the Fe/2OG halogenase, SyrB2, remain stably bound to its carrier protein substrate (l-aminoacyl-S-SyrB1), whereas the corresponding complexes harboring transition metals (Fe, Mn) in lower oxidation states dissociate. In the well-studied taurine:2OG dioxygenase (TauD), the disposition of the substrate C-H bond relative to the vanadyl ion defined by pulse electron paramagnetic resonance methods is consistent with the crystal structure of the reactant complex and computational models of the ferryl state. Vanadyl substitution may thus afford access to structural details of the key ferryl intermediates in this important enzyme class.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 13382-13389 |
| Number of pages | 8 |
| Journal | Inorganic Chemistry |
| Volume | 56 |
| Issue number | 21 |
| DOIs | |
| State | Published - Nov 6 2017 |
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All Science Journal Classification (ASJC) codes
- Physical and Theoretical Chemistry
- Inorganic Chemistry
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Vanadyl as a Stable Structural Mimic of Reactive Ferryl Intermediates in Mononuclear Nonheme-Iron Enzymes. / Martinie, Ryan J.; Pollock, Christopher J.; Matthews, Megan L.; Bollinger, Jr., Joseph M.; Krebs, Carsten; Silakov, Alexey.
In: Inorganic Chemistry, Vol. 56, No. 21, 06.11.2017, p. 13382-13389.Research output: Contribution to journal › Article
TY - JOUR
T1 - Vanadyl as a Stable Structural Mimic of Reactive Ferryl Intermediates in Mononuclear Nonheme-Iron Enzymes
AU - Martinie, Ryan J.
AU - Pollock, Christopher J.
AU - Matthews, Megan L.
AU - Bollinger, Jr., Joseph M.
AU - Krebs, Carsten
AU - Silakov, Alexey
PY - 2017/11/6
Y1 - 2017/11/6
N2 - The iron(II)- and 2-(oxo)glutarate-dependent (Fe/2OG) oxygenases catalyze an array of challenging transformations via a common iron(IV)-oxo (ferryl) intermediate, which in most cases abstracts hydrogen (H•) from an aliphatic carbon of the substrate. Although it has been shown that the relative disposition of the Fe-O and C-H bonds can control the rate of H• abstraction and fate of the resultant substrate radical, there remains a paucity of structural information on the actual ferryl states, owing to their high reactivity. We demonstrate here that the stable vanadyl ion [(VIV-oxo)2+] binds along with 2OG or its decarboxylation product, succinate, in the active site of two different Fe/2OG enzymes to faithfully mimic their transient ferryl states. Both ferryl and vanadyl complexes of the Fe/2OG halogenase, SyrB2, remain stably bound to its carrier protein substrate (l-aminoacyl-S-SyrB1), whereas the corresponding complexes harboring transition metals (Fe, Mn) in lower oxidation states dissociate. In the well-studied taurine:2OG dioxygenase (TauD), the disposition of the substrate C-H bond relative to the vanadyl ion defined by pulse electron paramagnetic resonance methods is consistent with the crystal structure of the reactant complex and computational models of the ferryl state. Vanadyl substitution may thus afford access to structural details of the key ferryl intermediates in this important enzyme class.
AB - The iron(II)- and 2-(oxo)glutarate-dependent (Fe/2OG) oxygenases catalyze an array of challenging transformations via a common iron(IV)-oxo (ferryl) intermediate, which in most cases abstracts hydrogen (H•) from an aliphatic carbon of the substrate. Although it has been shown that the relative disposition of the Fe-O and C-H bonds can control the rate of H• abstraction and fate of the resultant substrate radical, there remains a paucity of structural information on the actual ferryl states, owing to their high reactivity. We demonstrate here that the stable vanadyl ion [(VIV-oxo)2+] binds along with 2OG or its decarboxylation product, succinate, in the active site of two different Fe/2OG enzymes to faithfully mimic their transient ferryl states. Both ferryl and vanadyl complexes of the Fe/2OG halogenase, SyrB2, remain stably bound to its carrier protein substrate (l-aminoacyl-S-SyrB1), whereas the corresponding complexes harboring transition metals (Fe, Mn) in lower oxidation states dissociate. In the well-studied taurine:2OG dioxygenase (TauD), the disposition of the substrate C-H bond relative to the vanadyl ion defined by pulse electron paramagnetic resonance methods is consistent with the crystal structure of the reactant complex and computational models of the ferryl state. Vanadyl substitution may thus afford access to structural details of the key ferryl intermediates in this important enzyme class.
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U2 - 10.1021/acs.inorgchem.7b02113
DO - 10.1021/acs.inorgchem.7b02113
M3 - Article
C2 - 28960972
AN - SCOPUS:85033375903
VL - 56
SP - 13382
EP - 13389
JO - Inorganic Chemistry
JF - Inorganic Chemistry
SN - 0020-1669
IS - 21
ER -