Myoglobin: The hydrogen atom of biology and a paradigm of complexity

Frauenfelder, Hans; McMahon, Benjamin H.; Fenimore, Paul W.

doi:10.1073/pnas.1633688100

Cited by 201 publications

(166 citation statements)

References 29 publications

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“…In particular, NADH-metHb andmetMb reductases catalyze the conversion of heme-Fe(III) to heme-Fe(II) in vivo. As a matter of fact, the enzymatic hemeFe(III) reduction is the rate-limiting step of the whole process, this representing a severe limitation for the efficiency of these mechanisms in vivo (4,28,(35)(36)(37)(38)(39)(40)(41)(42)(43).…”

mentioning

confidence: 99%

Catalytic peroxidation of nitrogen monoxide and peroxynitrite by globins

et al. 2008

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SummaryGlobins are generally considered as carriers of diatomic gaseous ligands (e.g., O 2 and NO) in metazoa. Recently, the (pseudo-)enzymatic activity of globins towards reactive nitrogen and oxygen species has been elucidated. In particular, some globins (e.g., hemoglobin and myoglobin) catalyze the enzymatic scavenging of NO and peroxynitrite in the presence of H 2 O 2 . Indeed, H 2 O 2 oxidizes some globins leading to the formation of water and of the heme-protein ferryl derivative, which, in turn, oxidizes NO and peroxynitrite leading to the formation of the globin ferric species, NO 2 2 , and NO 3 2 . Here, we hypothesize that NO, peroxynitrite, and H 2 O 2 are co-substrates for the peroxidase activity of some globins, this catalytic activity was reported in 1900 for the first time, even though the substrates have never been identified firmly up to now. The hemoglobin (Hb) superfamily includes several hemeproteins, generally referred to as globins, which are found in all kingdoms of living organisms (1, 2). Globin functions have been the subject of active debate, in addition to dioxygen transport and storage. Several functions have been proposed recently, including control of nitrogen monoxide levels, O 2 sensing, and dehaloperoxidase activity (3-15).Globins share physical, spectroscopic, and chemical similarities with peroxidases (16,17). In fact, as demonstrated first in 1900 (18), Hb reacts readily with hydrogen peroxide (H 2 O 2 ). In 1923, the peroxidase activity of Hb has been reported (19), and in 1938, the modulation of the peroxidase activity of Hb by haptoglobin has been demonstrated (20). The reaction of myoglobin (Mb) with H 2 O 2 , on the other hand, apparently was not considered until 1952 (21), and the ability of Mb to catalyze peroxide oxidation of substrates was not reported until 1955 (22). Upon reaction with H 2 O 2 , Mb and Hb form the cytotoxic ferryl derivative (heme-Fe(IV)¼ ¼O), which is similar to compound II formed by peroxidases (23, 24). Heme-Fe(IV)¼ ¼O is able to oxidize a wide range of reducing substrates, such as phenols and aromatic amines, even though substrate peroxidation by Hb and Mb is far less efficient than that of peroxidases (24, 25), ruling out the possibility that the potential peroxidase activity of Hb and Mb is exerted on this class of substrates under normal conditions.Here, we hypothesize that the capability of some globins (e.g., Hb and Mb) to form a compound II-like species under oxidative stress may be actually exploited to avoid the building up of NO and peroxynitrite, 1 which can be then identified as the 'true' substrates for the peroxidase activity of Hb and Mb.Heme-proteins share the ability of detoxifying nitrogen reactive species, for example, NO. Even though leukocyte peroxi- 1 The term peroxynitrite is used in the text to refer generically to both ONOO 2 and its conjugated acid HOONO (38).

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Catalytic peroxidation of nitrogen monoxide and peroxynitrite by globins

et al. 2008

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“…Динамика широкого класса физически важных сложных на-носкопических систем (стёкла, кластеры, полимеры) описывается случайным блужданием на сложном энергетическом ландшаф-те [153], [156], [264], [267]. Ландшафтом называется непрерывная вещественнозначная функция (энергия) на области в R N .…”

Section: метод межбассейновой кинетикиunclassified

“…Связывание Mb-CO. Получаемые при помощи при-менения p-адических методов результаты для динамики связыва-ния миоглобина с CO [112] совпадают с данными спектроскопи-ческих экспериментов. Следует отметить, что модель связывания миоглобина с CO играет в физике белка основополагающую роль, аналогичную роли модели атома водорода в квантовой механи-ке [156].…”

Section: ультраметрическая диффузияunclassified

“…4) Следующее рассматриваемое нами приложение ультрамет-рики в физике связано с моделями случайного блуждания на сложных энергетических ландшафтах [153], [156], [264], [267]. Та-кие модели актуальны для описания динамики сложных макро-молекул, таких, как белки (в рамках релаксационной концепции динамики белка [9]).…”

Section: Introductionunclassified

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Козырев¹

2008

Sovrem. Probl. Mat.

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“…Here, the structural and functional properties of Nbs, Hs-α 1 -m and NPs are examined in parallel with those of sperm whale (Physeter catodon) myoglobin (Pc-Mb), which is generally taken as the molecular model of monomeric globins (39).…”

Section: Introductionmentioning

confidence: 99%

Nitrophorins and nitrobindins: structure and function

Ascenzi

Masi

et al. 2017

Biomolecular Concepts

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Classical all α-helical globins are present in all living organisms and are ordered in three lineages: (i) flavohemoglobins and single domain globins, (ii) protoglobins and globin coupled sensors and (iii) truncated hemoglobins, displaying the 3/3 or the 2/2 all α-helical fold. However, over the last two decades, all β-barrel and mixed α-helical-β-barrel heme-proteins displaying hemebased functional properties (e.g. ligand binding, transport and sensing) closely similar to those of all α-helical globins have been reported. Monomeric nitrophorins (NPs) and α 1 -microglobulin (α 1 -m), belonging to the lipocalin superfamily and nitrobindins (Nbs) represent prototypical heme-proteins displaying the all β-barrel and mixed α-helical-β-barrel folds. NPs are confined to the Reduviidae and Cimicidae families of Heteroptera, whereas α 1 -m and Nbs constitute heme-protein families spanning bacteria to Homo sapiens. The structural organization and the reactivity of the stable ferric solvent-exposed heme-Fe atom suggest that NPs and Nbs are devoted to NO transport, storage and sensing, whereas Hs-α 1 -m participates in heme metabolism. Here, the structural and functional properties of NPs and Nbs are reviewed in parallel with those of sperm whale myoglobin, which is generally taken as the prototype of monomeric globins.

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Myoglobin: The hydrogen atom of biology and a paradigm of complexity

Cited by 201 publications

References 29 publications

Catalytic peroxidation of nitrogen monoxide and peroxynitrite by globins

Catalytic peroxidation of nitrogen monoxide and peroxynitrite by globins

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Nitrophorins and nitrobindins: structure and function

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