Oxidizing Intermediates from the Sterically Hindered Iron Salen Complexes Related to the Oxygen Activation by Nonheme Iron Enzymes

2005 ◽  
Vol 44 (22) ◽  
pp. 8156-8166 ◽  
Author(s):  
Takuya Kurahashi ◽  
Yoshio Kobayashi ◽  
Shigenori Nagatomo ◽  
Takehiko Tosha ◽  
Teizo Kitagawa ◽  
...  
Keyword(s):  
Oxygen Activation ◽  
Nonheme Iron ◽  
Nonheme Iron Enzymes ◽  
Salen Complexes ◽  
Iron Enzymes ◽  
Sterically Hindered

scholarly journals Direct coordination of pterin to FeII enables neurotransmitter biosynthesis in the pterin-dependent hydroxylases

2021 ◽  
Vol 118 (15) ◽  
pp. e2022379118
Author(s):  
Shyam R. Iyer ◽  
Kasper D. Tidemand ◽  
Jeffrey T. Babicz ◽  
Ariel B. Jacobs ◽  
Leland B. Gee ◽  
...  
Keyword(s):  
Active Site ◽  
Tryptophan Hydroxylase ◽  
Activation Barrier ◽  
Magnetic Circular Dichroism ◽  
Aromatic Amino Acids ◽  
Oxygen Activation ◽  
Nonheme Iron ◽  
Nonheme Iron Enzymes ◽  
Iron Enzymes ◽  
Pterin Cofactor

The pterin-dependent nonheme iron enzymes hydroxylate aromatic amino acids to perform the biosynthesis of neurotransmitters to maintain proper brain function. These enzymes activate oxygen using a pterin cofactor and an aromatic amino acid substrate bound to the FeII active site to form a highly reactive FeIV = O species that initiates substrate oxidation. In this study, using tryptophan hydroxylase, we have kinetically generated a pre-FeIV = O intermediate and characterized its structure as a FeII-peroxy-pterin species using absorption, Mössbauer, resonance Raman, and nuclear resonance vibrational spectroscopies. From parallel characterization of the pterin cofactor and tryptophan substrate–bound ternary FeII active site before the O2 reaction (including magnetic circular dichroism spectroscopy), these studies both experimentally define the mechanism of FeIV = O formation and demonstrate that the carbonyl functional group on the pterin is directly coordinated to the FeII site in both the ternary complex and the peroxo intermediate. Reaction coordinate calculations predict a 14 kcal/mol reduction in the oxygen activation barrier due to the direct binding of the pterin carbonyl to the FeII site, as this interaction provides an orbital pathway for efficient electron transfer from the pterin cofactor to the iron center. This direct coordination of the pterin cofactor enables the biological function of the pterin-dependent hydroxylases and demonstrates a unified mechanism for oxygen activation by the cofactor-dependent nonheme iron enzymes.

scholarly journals Evaluation of a concerted vs. sequential oxygen activation mechanism in α-ketoglutarate–dependent nonheme ferrous enzymes

2020 ◽  
Vol 117 (10) ◽  
pp. 5152-5159 ◽  
Author(s):  
Serra Goudarzi ◽  
Shyam R. Iyer ◽  
Jeffrey T. Babicz ◽  
James J. Yan ◽  
Günther H. J. Peters ◽  
...  
Keyword(s):  
Substrate Binding ◽  
Oxygen Activation ◽  
Ring Expansion ◽  
Nonheme Iron ◽  
Activation Mechanism ◽  
Concerted Mechanism ◽  
Cofactor Binding ◽  
Nonheme Iron Enzymes ◽  
Iron Enzymes ◽  
Sequential Mechanism

Determining the requirements for efficient oxygen (O2) activation is key to understanding how enzymes maintain efficacy and mitigate unproductive, often detrimental reactivity. For the α-ketoglutarate (αKG)–dependent nonheme iron enzymes, both a concerted mechanism (both cofactor and substrate binding prior to reaction with O2) and a sequential mechanism (cofactor binding and reaction with O2 precede substrate binding) have been proposed. Deacetoxycephalosporin C synthase (DAOCS) is an αKG-dependent nonheme iron enzyme for which both of these mechanisms have been invoked to generate an intermediate that catalyzes oxidative ring expansion of penicillin substrates in cephalosporin biosynthesis. Spectroscopy shows that, in contrast to other αKG-dependent enzymes (which are six coordinate when only αKG is bound to the FeII), αKG binding to FeII-DAOCS results in ∼45% five-coordinate sites that selectively react with O2 relative to the remaining six-coordinate sites. However, this reaction produces an FeIII species that does not catalyze productive ring expansion. Alternatively, simultaneous αKG and substrate binding to FeII-DAOCS produces five-coordinate sites that rapidly react with O2 to form an FeIV=O intermediate that then reacts with substrate to produce cephalosporin product. These results demonstrate that the concerted mechanism is operative in DAOCS and by extension, other nonheme iron enzymes.

Models for Amide Ligation in Nonheme Iron Enzymes

1997 ◽  
Vol 36 (24) ◽  
pp. 5424-5425 ◽  
Author(s):  
Sanjay K. Mandal ◽  
Lawrence Que
Keyword(s):  
Nonheme Iron ◽  
Nonheme Iron Enzymes ◽  
Iron Enzymes

scholarly journals Peroxo and oxo intermediates in mononuclear nonheme iron enzymes and related active sites

2009 ◽  
Vol 13 (1) ◽  
pp. 99-113 ◽  
Author(s):  
Edward I Solomon ◽  
Shaun D Wong ◽  
Lei V Liu ◽  
Andrea Decker ◽  
Marina S Chow
Keyword(s):  
Active Sites ◽  
Nonheme Iron ◽  
Nonheme Iron Enzymes ◽  
Iron Enzymes
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