The reaction mechanisms of heme catalases: An atomistic view by ab initio molecular dynamics

Alfonso‐Prieto, Mercedes; Vidossich, Pietro; Rovira, Carme

doi:10.1016/j.abb.2012.04.004

Cited by 68 publications

(51 citation statements)

References 76 publications

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“…A heme b-specific absorption Soret peak centered at ϭ 410 nm was observed for KatA WT ; this peak was shifted for KatA H56A ( ϭ 402 nm) and was essentially absent for KatA Y339A , indicating that the heme b environment is modified in KatA H56A , and it is abolished in KatA Y339A protein. These results were expected based on heme ligands predicted from the crystal structure (21,22).…”

Section: Resultssupporting

confidence: 54%

“…devoid of catalase activity. Based on the published crystal structure of H. pylori catalase, two residues are essential for catalysis as follows: the proximal Tyr-339, coordinated to the heme iron, and the distal His-56, essential for the formation of the main reaction intermediate, compound I (21,22). Therefore, two markerless chromosomal katA mutant versions, katA H56A and katA Y339A , were constructed in two H. pylori wild-type (WT) strains, strain 43504 and the mouse colonizing strain X47 (23).…”

Section: Resultsmentioning

confidence: 99%

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Helicobacter Catalase Devoid of Catalytic Activity Protects the Bacterium against Oxidative Stress

Benoit

Maier

2016

Journal of Biological Chemistry

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Catalase, a conserved and abundant enzyme found in all domains of life, dissipates the oxidant hydrogen peroxide (H 2 O 2 ). The gastric pathogen Helicobacter pylori undergoes host-mediated oxidant stress exposure, and its catalase contains oxidizable methionine (Met) residues. We hypothesized catalase may play a large stress-combating role independent of its classical catalytic one, namely quenching harmful oxidants through its recyclable Met residues, resulting in oxidant protection to the bacterium. Two Helicobacter mutant strains (katA H56A and katA Y339A ) containing catalase without enzyme activity but that retain all Met residues were created. These strains were much more resistant to oxidants than a catalasedeletion mutant strain. The quenching ability of the altered versions was shown, whereby oxidant-stressed (HOCl-exposed) Helicobacter retained viability even upon extracellular addition of the inactive versions of catalase, in contrast to cells receiving HOCl alone. The importance of the methionine-mediated quenching to the pathogen residing in the oxidant-rich gastric mucus was studied. In contrast to a catalase-null strain, both site-change mutants proficiently colonized the murine gastric mucosa, suggesting that the amino acid composition-dependent oxidant-quenching role of catalase is more important than the well described H 2 O 2 -dissipating catalytic role. Over 100 years after the discovery of catalase, these findings reveal a new nonenzymatic protective mechanism of action for the ubiquitous enzyme.Catalase was described over 100 years ago (1), and the enzyme's role clearly is to detoxify H 2 O 2 by converting it into H 2 O and O 2 . It is one of he most abundant proteins in cells, and it is present in most organisms, including in both plant and animal cells (2). It is oftentimes a highly expressed protein. For example, in the gastric pathogen Helicobacter pylori, catalase (KatA) levels are estimated to be 4 -5% of the total protein content (3), and the katA gene is one of the most highly expressed genes in H. pylori cells recovered from the human stomach (4). HOCl-mediated oxidation of six identified Met residues in H. pylori KatA leads to methionine sulfoxide formation (Met-O), 2 protein oligomerization, and loss of catalase activity (3). Most organisms, including Helicobacter, possess a peptide repair enzyme, methionine sulfoxide reductase (Msr), that reduces Met-O back to Met in certain oxidation-susceptible Msr-targeted proteins (5, 6). This Msr-mediated repair (along with added GroEL/ES) returns most of the catalase activity (3). Although the identified protein targets of repair are few among the total of all organisms, some of these repair targets are themselves stress-combating enzymes.Purified KatA and Msr enzymes were shown to physically interact (6), and this interaction resulted in Msr-mediated repair of five out of the six oxidized KatA Met residues (3). In addition, H. pylori KatA is ubiquitous, present in both the cytoplasm and in the periplasm and on the cell surface as well as...

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Section: Resultssupporting

confidence: 54%

Section: Resultsmentioning

confidence: 99%

Helicobacter Catalase Devoid of Catalytic Activity Protects the Bacterium against Oxidative Stress

Benoit

Maier

2016

Journal of Biological Chemistry

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“…Catalases are heme-containing enzymes (34). Mammalian Prx1 was previously identified as heme-binding protein 23 kDa (HBP23) (10,35), and a bacterial 2-Cys peroxiredoxin alkyl hydroperoxide reductase C (AhpC) was also reported to be able to bind heme (36), although heme binding is non-essential to their functions.…”

Section: Discussionmentioning

confidence: 99%

Cysteine-independent Catalase-like Activity of Vertebrate Peroxiredoxin 1 (Prx1)

Sun

Dong

Zhao

et al. 2015

Journal of Biological Chemistry

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Background: Peroxiredoxin (Prx) was previously known only as a Cys-dependent thioredoxin. Results: Cys-independent catalase-like activity was observed in two vertebrate Prx1 proteins. Conclusion: Prx1 possesses dual antioxidant activities with varied affinities toward H 2 O 2 . Significance: This discovery extends our knowledge on Prx1 and provides new opportunities to further study the biological roles of this family of antioxidants.

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“…This method has proven highly efficacious for other heme proteins including the catalases and peroxides, [17][18][19][20][21][22] and has been the subject of several excellent reviews. 23,24 The thermodynamics of Cpd I and FeOHPor reactivity are thus characterized in a context that is more physically realistic than zero-temperature quantum chemical calculations, while simultaneously providing kinetic data including the lifetime for the highly reactive hydroxyiron species.…”

Section: Introductionmentioning

confidence: 99%

Ab initio dynamics of the cytochrome P450 hydroxylation reaction

Elenewski

Hackett

2015

The Journal of Chemical Physics

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The iron(IV)-oxo porphyrin π-cation radical known as Compound I is the primary oxidant within the cytochromes P450, allowing these enzymes to affect the substrate hydroxylation. In the course of this reaction, a hydrogen atom is abstracted from the substrate to generate hydroxyiron(IV) porphyrin and a substrate-centered radical. The hydroxy radical then rebounds from the iron to the substrate, yielding the hydroxylated product. While Compound I has succumbed to theoretical and spectroscopic characterization, the associated hydroxyiron species is elusive as a consequence of its very short lifetime, for which there are no quantitative estimates. To ascertain the physical mechanism underlying substrate hydroxylation and probe this timescale, ab initio molecular dynamics simulations and free energy calculations are performed for a model of Compound I catalysis. Semiclassical estimates based on these calculations reveal the hydrogen atom abstraction step to be extremely fast, kinetically comparable to enzymes such as carbonic anhydrase. Using an ensemble of ab initio simulations, the resultant hydroxyiron species is found to have a similarly short lifetime, ranging between 300 fs and 3600 fs, putatively depending on the enzyme active site architecture. The addition of tunneling corrections to these rates suggests a strong contribution from nuclear quantum effects, which should accelerate every step of substrate hydroxylation by an order of magnitude. These observations have strong implications for the detection of individual hydroxylation intermediates during P450 catalysis. C 2015 AIP Publishing LLC. [http://dx

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The reaction mechanisms of heme catalases: An atomistic view by ab initio molecular dynamics

Cited by 68 publications

References 76 publications

Helicobacter Catalase Devoid of Catalytic Activity Protects the Bacterium against Oxidative Stress

Helicobacter Catalase Devoid of Catalytic Activity Protects the Bacterium against Oxidative Stress

Cysteine-independent Catalase-like Activity of Vertebrate Peroxiredoxin 1 (Prx1)

Ab initio dynamics of the cytochrome P450 hydroxylation reaction

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