Chapter 1. Experimental and Computational Studies on the Catalytic Mechanism of Non-heme Iron Dioxygenases

Visser, Sam P. de

doi:10.1039/9781849732987-00001

Cited by 4 publications

(2 citation statements)

References 125 publications

(178 reference statements)

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“…Once the substrate is productively bound, there is evidence that HAT is the rate‐determining step during the demethylation reaction [5,24,30,31] . The rebound hydroxylation reaction is a relatively unexplored step in the demethylation reaction and is of interest because there is evidence that the lifetime of the Fe(III)−OH intermediate is sufficient for conformational changes in the substrate and enzyme [37] …”

Section: Introductionmentioning

confidence: 99%

“…[5,24,30,31] The rebound hydroxylation reaction is a relatively unexplored step in the demethylation reaction and is of interest because there is evidence that the lifetime of the Fe(III)À OH intermediate is sufficient for conformational changes in the substrate and enzyme. [37] Enzyme catalysis may be influenced by conformational dynamics, enabling sampling of catalytically productive config-…”

Section: Introductionmentioning

confidence: 99%

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Catalysis by KDM6 Histone Demethylases – A Synergy between the Non‐Heme Iron(II) Center, Second Coordination Sphere, and Long‐Range Interactions

Rifayee

Chaturvedi

Warner

et al. 2023

Chemistry A European J

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KDM6A (UTX) and KDM6B (JMJD3) are human nonheme Fe(II) and 2-oxoglutarate (2OG) dependent JmjC oxygenases that catalyze the demethylation of trimethylated lysine 27 in the N-terminal tail of histone H3, a post-translational modification that regulates transcription. A Combined Quantum Mechanics/ Molecular Mechanics (QM/MM) and Molecular Dynamics (MD) study on the catalytic mechanism of KDM6A/B reveals that the transition state for the ratelimiting hydrogen atom transfer (HAT) reaction in KDM6A catalysis is stabilized by polar (Asn217) and aromatic (Trp369)/non-polar (Pro274) residues in contrast to KDM4, KDM6B and KDM7 demethylases where charged residues (Glu, Arg, Asp) are involved. KDM6A employs both σand π-electron transfer pathways for HAT, whereas KDM6B employs the σ-electron pathway. Differences in hydrogen bonding of the Fe-chelating Glu252(KDM6B) contribute to the lower energy barriers in KDM6B vs. KDM6A. The study reveals a dependence of the activation barrier of the rebound hydroxylation on the FeÀ OÀ C angle in the transition state of KDM6A. Anti-correlation of the Zn-binding domain with the active site residues is a key factor distinguishing KDM6A/B from KDM7/ 4s. The results reveal the importance of communication between the Fe center, second coordination sphere, and long-range interactions in catalysis by KDMs and, by implication, other 2OG oxygenases.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Catalysis by KDM6 Histone Demethylases – A Synergy between the Non‐Heme Iron(II) Center, Second Coordination Sphere, and Long‐Range Interactions

Rifayee

Chaturvedi

Warner

et al. 2023

Chemistry A European J

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On the Catalytic Mechanism of (S)‐2‐Hydroxypropylphosphonic Acid Epoxidase (HppE): A Hybrid DFT Study

Miłaczewska

Brocławik

Borowski

2012

Chemistry A European J

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The mechanism of oxidative epoxidation catalyzed by HppE, which is the ultimate step in the biosynthesis of fosfomycin, was studied by using hybrid DFT quantum chemistry methods. An active site model used in the computations was based on the available crystal structure for the HppE-Fe(II)-(S)-HPP complex and it comprised first-shell ligands of iron as well as second-shell polar groups interacting with the substrates. The reaction energy profiles were constructed for three a priori plausible mechanisms proposed in the literature, and it was found that the most likely scenario for the native substrate, that is, (S)-HPP, involves generation of the reactive Fe(III)-O·/Fe(IV)=O species, which is responsible for the C-H bond-cleavage. At the subsequent reaction stage, the OH-rebound, which would lead to a hydroxylated product, is prevented by a fast protonation of the OH ligand and, as a result, ring closure is the energetically preferred step. For the R enantiomer of the substrate ((R)-HPP), which is oxidized to a keto product, comparable barrier heights were found for the C-H bond activation by both the Fe(III)-O(2)· and Fe(IV)=O species.

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Enzymatic Bioremediation: Current Status, Challenges of Obtaining Process, and Applications

Okino‐Delgado

Zanutto-Elgui

Prado

et al. 2019

Microorganisms for Sustainability

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Chapter 1. Experimental and Computational Studies on the Catalytic Mechanism of Non-heme Iron Dioxygenases

Cited by 4 publications

References 125 publications

Catalysis by KDM6 Histone Demethylases – A Synergy between the Non‐Heme Iron(II) Center, Second Coordination Sphere, and Long‐Range Interactions

Catalysis by KDM6 Histone Demethylases – A Synergy between the Non‐Heme Iron(II) Center, Second Coordination Sphere, and Long‐Range Interactions

On the Catalytic Mechanism of (S)‐2‐Hydroxypropylphosphonic Acid Epoxidase (HppE): A Hybrid DFT Study

Enzymatic Bioremediation: Current Status, Challenges of Obtaining Process, and Applications

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