A Ferric–Peroxo Intermediate in the Oxidation of Heme by IsdI

Biochemistry ◽  
2015 ◽  
Vol 54 (16) ◽  
pp. 2613-2621 ◽  
Author(s):  
Shin-ichi J. Takayama ◽  
Slade A. Loutet ◽  
A. Grant Mauk ◽  
Michael E. P. Murphy
Keyword(s):  
Ferric Peroxo ◽  
Peroxo Intermediate

Formation of an End-On Ferric Peroxo Intermediate upon One-Electron Reduction of a Ferric Superoxo Heme

2010 ◽  
Vol 132 (11) ◽  
pp. 3672-3673 ◽  
Author(s):  
Jin-Gang Liu ◽  
Yuta Shimizu ◽  
Takehiro Ohta ◽  
Yoshinori Naruta
Keyword(s):  
Electron Reduction ◽  
Ferric Peroxo ◽  
Peroxo Intermediate

scholarly journals Unveiling the crucial intermediates in androgen production

2015 ◽  
Vol 112 (52) ◽  
pp. 15856-15861 ◽  
Author(s):  
Piotr J. Mak ◽  
Michael C. Gregory ◽  
Ilia G. Denisov ◽  
Stephen G. Sligar ◽  
James R. Kincaid
Keyword(s):  
Bond Cleavage ◽  
Nucleophilic Attack ◽  
Reaction Intermediates ◽  
Structural Determinants ◽  
Initial Product ◽  
Androgen Synthesis ◽  
Ferric Peroxo ◽  
Enzymatic Mechanisms ◽  
Primary Substrate

Ablation of androgen production through surgery is one strategy against prostate cancer, with the current focus placed on pharmaceutical intervention to restrict androgen synthesis selectively, an endeavor that could benefit from the enhanced understanding of enzymatic mechanisms that derives from characterization of key reaction intermediates. The multifunctional cytochrome P450 17A1 (CYP17A1) first catalyzes the typical hydroxylation of its primary substrate, pregnenolone (PREG) and then also orchestrates a remarkable C17–C20 bond cleavage (lyase) reaction, converting the 17-hydroxypregnenolone initial product to dehydroepiandrosterone, a process representing the first committed step in the biosynthesis of androgens. Now, we report the capture and structural characterization of intermediates produced during this lyase step: an initial peroxo-anion intermediate, poised for nucleophilic attack on the C20 position by a substrate-associated H-bond, and the crucial ferric peroxo-hemiacetal intermediate that precedes carbon–carbon (C-C) bond cleavage. These studies provide a rare glimpse at the actual structural determinants of a chemical transformation that carries profound physiological consequences.

scholarly journals Do two oxidants (ferric-peroxo and ferryl-oxo species) act in the biosynthesis of estrogens? A DFT calculation

RSC Advances ◽  
2018 ◽  
Vol 8 (27) ◽  
pp. 15196-15201 ◽  
Author(s):  
Xiang-Yun Wang ◽  
Hui-Min Yan ◽  
Yan-Li Han ◽  
Zhu-Xia Zhang ◽  
Xiao-Yun Zhang ◽  
...  
Keyword(s):  
Density Functional Theory ◽  
Density Functional ◽  
Dft Calculation ◽  
Density Functional Theory Calculations ◽  
Functional Theory ◽  
Two Oxidants ◽  
Ferric Peroxo

Density functional theory calculations were performed in order to reveal the mysterious catalytic step of the biosynthesis of estrogens.

scholarly journals Isolation of a Ru(iv) side-on peroxo intermediate in the water oxidation reaction

2021 ◽  
Author(s):  
Carla Casadevall ◽  
Vlad Martin-Diaconescu ◽  
Wesley R. Browne ◽  
Sergio Fernández ◽  
Federico Franco ◽  
...  
Keyword(s):  
Water Oxidation ◽  
Oxidation Reaction ◽  
Peroxo Intermediate

Mössbauer Studies of the Formation and Reactivity of a Quasi-Stable Peroxo Intermediate of Stearoyl-Acyl Carrier Protein Δ9-Desaturase†

Biochemistry ◽  
1999 ◽  
Vol 38 (38) ◽  
pp. 12197-12204 ◽  
Author(s):  
John A. Broadwater ◽  
Catalina Achim ◽  
Eckard Münck ◽  
Brian G. Fox
Keyword(s):  
Acyl Carrier Protein ◽  
Carrier Protein ◽  
Mössbauer Studies ◽  
Δ9 Desaturase ◽  
Peroxo Intermediate

scholarly journals Crystal structures of alkylperoxo and anhydride intermediates in an intradiol ring-cleaving dioxygenase

2014 ◽  
Vol 112 (2) ◽  
pp. 388-393 ◽  
Author(s):  
Cory J. Knoot ◽  
Vincent M. Purpero ◽  
John D. Lipscomb
Keyword(s):  
Ring Cleavage ◽  
Site Specificity ◽  
Computational Studies ◽  
Structural Comparison ◽  
Alternative Substrate ◽  
Extradiol Dioxygenase ◽  
X Ray ◽  
Solution Studies ◽  
Extradiol Dioxygenases ◽  
Peroxo Intermediate

Intradiol aromatic ring-cleaving dioxygenases use an active site, nonheme Fe3+ to activate O2 and catecholic substrates for reaction. The inability of Fe3+ to directly bind O2 presents a mechanistic conundrum. The reaction mechanism of protocatechuate 3,4-dioxygenase is investigated here using the alternative substrate 4-fluorocatechol. This substrate is found to slow the reaction at several steps throughout the mechanistic cycle, allowing the intermediates to be detected in solution studies. When the reaction was initiated in an enzyme crystal, it was found to halt at one of two intermediates depending on the pH of the surrounding solution. The X-ray crystal structure of the intermediate at pH 6.5 revealed the key alkylperoxo-Fe3+ species, and the anhydride-Fe3+ intermediate was found for a crystal reacted at pH 8.5. Intermediates of these types have not been structurally characterized for intradiol dioxygenases, and they validate four decades of spectroscopic, kinetic, and computational studies. In contrast to our similar in crystallo crystallographic studies of an Fe2+-containing extradiol dioxygenase, no evidence for a superoxo or peroxo intermediate preceding the alkylperoxo was found. This observation and the lack of spectroscopic evidence for an Fe2+ intermediate that could bind O2 are consistent with concerted formation of the alkylperoxo followed by Criegee rearrangement to yield the anhydride and ultimately ring-opened product. Structural comparison of the alkylperoxo intermediates from the intra- and extradiol dioxygenases provides a rationale for site specificity of ring cleavage.

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