Peroxidase activity enhancement of myoglobin by two cooperative distal histidines and a channel to the heme pocket

Wu, Lei-Bin; Du, Ke; Nie, Changming; Gao, Shu‐Qin; Wen, Ge; Tan, Xiangshi; Lin, Ying‐Wu

doi:10.1016/j.molcatb.2016.08.018

Cited by 8 publications

(7 citation statements)

References 40 publications

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“…Many heme-containing proteins and peptide assemblies display peroxidase activity. In fact, myoglobin has been demonstrated to yield peroxidase activity, and, as mentioned earlier, cytochrome c in the presence of cancerous cells has been proposed to change from an electron transfer protein to a peroxidase . Here, we demonstrate a similar phenomenon in that, with the same peptide ( AH Heme ), we can modulate the reactivity just by changing the morphology from micelles to fibers, a potentially useful mechanism in a peptide amphiphile material.…”

Section: Resultssupporting

confidence: 74%

Control of Heme Coordination and Catalytic Activity by Conformational Changes in Peptide–Amphiphile Assemblies

2017

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Self-assembling peptide materials have gained significant attention, due to well-demonstrated applications, but they are functionally underutilized. To advance their utility, we use noncovalent interactions to incorporate the biological cofactor heme-B for catalysis. Heme-proteins achieve differing functions through structural and coordinative variations. Here, we replicate this phenomenon by highlighting changes in heme reactivity as a function of coordination, sequence, and morphology (micelles versus fibers) in a series of simple peptide amphiphiles with the sequence c16-xyLK-COH where c16 is a palmitoyl moiety and xy represents the heme binding region: AA, AH, HH, and MH. The morphology of this peptide series is characterized using transmission electron and atomic force microscopies as well as dynamic light scattering. Within this small library of peptide constructs, we show that three spectroscopically (UV/visible and electron paramagnetic resonance) distinct heme environments were generated: noncoordinated/embedded high-spin, five-coordinate high-spin, and six-coordinate low-spin. The resulting material's functional dependence on sequence and supramolecular morphology is highlighted 2-fold. First, the heme active site binds carbon monoxide in both micelles and fibers, demonstrating that the heme active site in both morphologies is accessible to small molecules for catalysis. Second, peroxidase activity was observed in heme-containing micelles yet was significantly reduced in heme-containing fibers. We briefly discuss the implications these findings have in the production of functional, self-assembling peptide materials.

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Section: Resultssupporting

confidence: 74%

Control of Heme Coordination and Catalytic Activity by Conformational Changes in Peptide–Amphiphile Assemblies

2017

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“…Therefore, if the DNA aptamer interacts with the heme-surrounding positively-charged surface of myoglobin, the aptamer could affect myoglobin itself, upregulating peroxidation, as AES. There are reports on the improvement of peroxidase activity of myoglobin by the introduction of a few histidine residues near the sixth coordination site of Fe in the heme ( 33 , 35 , 36 ), which corresponds to our hypothesis. Additionally, ribosome, a complex of ribozyme and the ribosomal protein, might coordinately withdraw a proton from the surrounding nucleic and amino acids ( 37 ).…”

Section: Introductionsupporting

confidence: 84%

G-quadruplex-forming aptamer enhances the peroxidase activity of myoglobin against luminol

Tsukakoshi

Yamagishi

Kanazashi

et al. 2021

Nucleic Acids Research

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Aptamers can control the biological functions of enzymes, thereby facilitating the development of novel biosensors. While aptamers that inhibit catalytic reactions of enzymes were found and used as signal transducers to sense target molecules in biosensors, no aptamers that amplify enzymatic activity have been identified. In this study, we report G-quadruplex (G4)-forming DNA aptamers that upregulate the peroxidase activity in myoglobin specifically for luminol. Using in vitro selection, one G4-forming aptamer that enhanced chemiluminescence from luminol by myoglobin's peroxidase activity was discovered. Through our strategy—in silico maturation, which is a genetic algorithm-aided sequence manipulation method, the enhancing activity of the aptamer was improved by introducing mutations to the aptamer sequences. The best aptamer conserved the parallel G4 property with over 300-times higher luminol chemiluminescence from peroxidase activity more than myoglobin alone at an optimal pH of 5.0. Furthermore, using hemin and hemin-binding aptamers, we demonstrated that the binding property of the G4 aptamers to heme in myoglobin might be necessary to exert the enhancing effect. Structure determination for one of the aptamers revealed a parallel-type G4 structure with propeller-like loops, which might be useful for a rational design of aptasensors utilizing the G4 aptamer-myoglobin pair.

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“…Additionally, three strategies have been employed to study and enhance catalysis in these systems. The first approach is to mimic the structural features of a desired native enzyme, such as the His-Arg pair or the positioning of the distal His in peroxidases. , The second is to employ SDM at SCS residues surrounding the active site to vary structural features such as sterics, polarization, and H-bonding to tune the activity. The third entails using directed evolution to repurpose a native heme protein for new, non-native functions.…”

Section: Discussionmentioning

confidence: 99%

“…As another corroboration of the importance of the proper positioning of the distal His in Mb for peroxidase functions, the L29H/H64V mutant exhibited a ∼3–6 slower reaction rate with H 2 O 2 relative to the native Mb as the imidazole of His29 is too far away to interact with the H 2 O 2 substrate . As another example of mimicking the structural features of the native peroxidase, Wu, et al found that introduction of two His residues near the active site through the L29H/F43H double mutant produces a SCS resembling the His-Arg pair that is frequently observed in native peroxidases . An additional H64A mutation further opened a channel to the heme active center, positively influencing the peroxidase activity.…”

Section: Catalysis Beyond the Primary Coordination Sphere By Heme Pro...mentioning

confidence: 99%

Designing Artificial Metalloenzymes by Tuning of the Environment beyond the Primary Coordination Sphere

et al. 2022

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Metalloenzymes catalyze a variety of reactions using a limited number of natural amino acids and metallocofactors. Therefore, the environment beyond the primary coordination sphere must play an important role in both conferring and tuning their phenomenal catalytic properties, enabling active sites with otherwise similar primary coordination environments to perform a diverse array of biological functions. However, since the interactions beyond the primary coordination sphere are numerous and weak, it has been difficult to pinpoint structural features responsible for the tuning of activities of native enzymes. Designing artificial metalloenzymes (ArMs) offers an excellent basis to elucidate the roles of these interactions and to further develop practical biological catalysts. In this review, we highlight how the secondary coordination spheres of ArMs influence metal binding and catalysis, with particular focus on the use of native protein scaffolds as templates for the design of ArMs by either rational design aided by computational modeling, directed evolution, or a combination of both approaches. In describing successes in designing heme, nonheme Fe, and Cu metalloenzymes, heteronuclear metalloenzymes containing heme, and those ArMs containing other metal centers (including those with non-native metal ions and metallocofactors), we have summarized insights gained on how careful controls of the interactions in the secondary coordination sphere, including hydrophobic and hydrogen bonding interactions, allow the generation and tuning of these respective systems to approach, rival, and, in a few cases, exceed those of native enzymes. We have also provided an outlook on the remaining challenges in the field and future directions that will allow for a deeper understanding of the secondary coordination sphere a deeper understanding of the secondary coordintion sphere to be gained, and in turn to guide the design of a broader and more efficient variety of ArMs.

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Peroxidase activity enhancement of myoglobin by two cooperative distal histidines and a channel to the heme pocket

Cited by 8 publications

References 40 publications

Control of Heme Coordination and Catalytic Activity by Conformational Changes in Peptide–Amphiphile Assemblies

Control of Heme Coordination and Catalytic Activity by Conformational Changes in Peptide–Amphiphile Assemblies

G-quadruplex-forming aptamer enhances the peroxidase activity of myoglobin against luminol

Designing Artificial Metalloenzymes by Tuning of the Environment beyond the Primary Coordination Sphere

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