Heme: From quantum spin crossover to oxygen manager of life

Kepp, Kasper Planeta

doi:10.1016/j.ccr.2016.08.008

Cited by 56 publications

(60 citation statements)

References 210 publications

(222 reference statements)

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“…Agreement of our and earlier Kβ data of MB/HB (45) supports the spin state changes. For the hemes and porphyrins, our Kβ main-line, ctv/vtc, and (TD)DFT/ CASSCF data revealed ferrous HS (deoxy, 2) or LS (carboxy, 1) and ferric HS (3) species (1,40), emphasizing the method´s sensitivity for valence and spin-state discrimination. Further discussion of relations between the XAS/XES data and iron spin states is given in SI Appendix.…”

Section: Discussionmentioning

confidence: 99%

“…Scrutiny over decades has been devoted to the heme chemistry in myoglobin (MB) and hemoglobin (HB) proteins of vertebrates ( Fig. 1), which is the basis for their vital O 2 -transporting properties (1)(2)(3)(4)(5). Renewed interest in the topic stems from ongoing discovery of globins in plants and microorganisms, which further extends the spectrum of biological functions (6)(7)(8).…”

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confidence: 99%

“…The possible resonance character of these Lewis structures was emphasized already in early theory work (18). Density functional theory (DFT), providing access to experimental observables (19,20), and complete-active-space selfconsistent-field (CASSCF) quantum chemical calculations facilitated description of many structural and spectroscopic features of the O 2 bonding (1,18). A McClure-like oxy (21), and Pauling/ Weiss formulations have emerged, to some extent depending on model terms used to interpret multiconfigurational wavefunctions (21)(22)(23).…”

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confidence: 99%

“…A McClure-like oxy (21), and Pauling/ Weiss formulations have emerged, to some extent depending on model terms used to interpret multiconfigurational wavefunctions (21)(22)(23). Modification of porphyrin groups and heme/ligand geometries by the protein matrix and hydrogen bonding may bias the Fe-O 2 interaction to the diverse functions (1,(24)(25)(26).…”

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confidence: 99%

“…heme cofactor | X-ray spectroscopy | quantum chemistry | O 2 binding | spin state P roteins binding an iron-porphyrin (heme) cofactor are nature's versatile dioxygen (O 2 ) managers, facilitating O 2 sensing, transport, activation chemistry, and catalysis (1). Scrutiny over decades has been devoted to the heme chemistry in myoglobin (MB) and hemoglobin (HB) proteins of vertebrates ( Fig.…”

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confidence: 99%

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Effective intermediate-spin iron in O ₂ -transporting heme proteins

Schuth

Mebs

Huwald

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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Proteins carrying an iron-porphyrin (heme) cofactor are essential for biological O2 management. The nature of Fe-O2 bonding in hemoproteins is debated for decades. We used energy-sampling and rapid-scan X-ray Kβ emission and K-edge absorption spectroscopy as well as quantum chemistry to determine molecular and electronic structures of unligated (deoxy), CO-inhibited (carboxy), and O2-bound (oxy) hemes in myoglobin (MB) and hemoglobin (HB) solutions and in porphyrin compounds at 20–260 K. Similar metrical and spectral features revealed analogous heme sites in MB and HB and the absence of low-spin (LS) to high-spin (HS) conversion. Amplitudes of Kβ main-line emission spectra were directly related to the formal unpaired Fe(d) spin count, indicating HS Fe(II) in deoxy and LS Fe(II) in carboxy. For oxy, two unpaired Fe(d) spins and, thus by definition, an intermediate-spin iron center, were revealed by our static and kinetic X-ray data, as supported by (time-dependent) density functional theory and complete-active-space self-consistent-field calculations. The emerging Fe-O2 bonding situation includes in essence a ferrous iron center, minor superoxide character of the noninnocent ligand, significant double-bond properties of the interaction, and three-center electron delocalization as in ozone. It resolves the apparently contradictory classical models of Pauling, Weiss, and McClure/Goddard into a unifying view of O2 bonding, tuned toward reversible oxygen transport.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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confidence: 99%

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confidence: 99%

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Effective intermediate-spin iron in O ₂ -transporting heme proteins

Schuth

Mebs

Huwald

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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First Principles Calculation of the Reaction Rates for Ligand Binding to Myoglobin: The Cases of NO and CO

Lábas

Menyhárd

Harvey

et al. 2018

Chemistry A European J

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Ligand binding by proteins is among the most fundamental processes in nature. Among these processes the binding of small gas molecules, such as O , CO and NO to heme proteins has traditionally received vivid interest, which was further boosted by their recently recognized significant role in gas sensing in the body. At the heart of the binding of these ligands to the heme group is the spinforbidden reaction between high-spin iron(II) and the ligand yielding a low-spin adduct. We use computational means to address the complete mechanism of CO and NO binding by myoglobin. Considering that it involves several steps occurring on different time scales, molecular dynamics simulations were performed to address the diffusion of the ligand through the enzyme, and DFT calculations in combination with statistical rate calculation to investigate the spin-forbidden reaction. The calculations yielded rate constants in qualitative agreement with experiments and revealed that the bottleneck of NO and CO binding is different; for NO, diffusion was found to be rate-limiting, whereas for CO, the spin-forbidden step is the slowest.

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Secondary Sphere Lewis Acid Activated Heme Superoxo Adducts Mimic Crucial Non‐Covalent Interactions in IDO/TDO Heme Dioxygenases

Tolbert,

Jayawardana,

Lee

et al. 2024

Chemistry A European J

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Heme enzymes play a central role in a medley of reactivities within a wide variety of crucial biological systems. Their active sites are highly decorated with pivotal evolutionarily optimized non‐covalent interactions that precisely choreograph their biological functionalities with specific regio‐, stereo‐, and chemo‐selectivities. Gaining a clear comprehension of how such weak interactions within the active sites control reactivity offers powerful information to be implemented into the design of future therapeutic agents that target these heme enzymes. To shed light on such critical details pertaining to tryptophan dioxygenating heme enzymes, this study investigates the indole dioxygenation reactivities of Lewis acid‐activated heme superoxo model systems, wherein an unprecedented kinetic behavior is revealed. In that, the activated heme superoxo adduct is observed to undergo indole dioxygenation with the intermediacy of a non‐covalently organized precursor complex, which forms prior to the rate‐limiting step of the overall reaction landscape. Spectroscopic and theoretical characterization of this precursor complex draws close parallels to the ternary complex of heme dioxygenases, which has been postulated to be of crucial importance for successful 2,3‐dioxygenative cleavage of indole moieties.

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Heme: From quantum spin crossover to oxygen manager of life

Cited by 56 publications

References 210 publications

Effective intermediate-spin iron in O ₂ -transporting heme proteins

Effective intermediate-spin iron in O ₂ -transporting heme proteins

First Principles Calculation of the Reaction Rates for Ligand Binding to Myoglobin: The Cases of NO and CO

Secondary Sphere Lewis Acid Activated Heme Superoxo Adducts Mimic Crucial Non‐Covalent Interactions in IDO/TDO Heme Dioxygenases

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Heme: From quantum spin crossover to oxygen manager of life

Cited by 56 publications

References 210 publications

Effective intermediate-spin iron in O 2 -transporting heme proteins

Effective intermediate-spin iron in O 2 -transporting heme proteins

First Principles Calculation of the Reaction Rates for Ligand Binding to Myoglobin: The Cases of NO and CO

Secondary Sphere Lewis Acid Activated Heme Superoxo Adducts Mimic Crucial Non‐Covalent Interactions in IDO/TDO Heme Dioxygenases

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Effective intermediate-spin iron in O ₂ -transporting heme proteins

Effective intermediate-spin iron in O ₂ -transporting heme proteins