The histidine brace: nature's copper alternative to haem?

Walton, Paul H.; Davies, G.J.; Díaz, Daniel E.; Franco-Cairo, João P

doi:10.1002/1873-3468.14579

Cited by 17 publications

(13 citation statements)

References 42 publications

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“…Due to effects on copper reactivity and on the geometry and hydrogen bonding networks of the catalytic center, this residue affects all aspects of LPMO reactivity including oxidase activity (H 2 O 2 production), peroxygenase activity, enzyme stability under turnover conditions, reduction and reoxidation of the active site copper, and radical formation, which may be related to a protective hole hopping mechanism. It has been pointed out that the histidine brace found in LPMOs may be “nature’s copper alternative to haem” . The present study shows that, just as the functionality of haem enzymes depends on subtle modulations in the environment surrounding the cofactor, the catalytic performance of the histidine brace is determined by its fine-tuned environment.…”

Section: Discussionmentioning

confidence: 52%

“…It has been pointed out that the histidine brace found in LPMOs may be "nature's copper alternative to haem". 78 The present study shows that, just as the functionality of haem enzymes depends on subtle modulations in the environment surrounding the cofactor, 79 the catalytic performance of the histidine brace is determined by its fine-tuned environment. Next to providing insight into LPMO functionality, the present results expand the knowledge base for LPMO-inspired design of synthetic Cu-catalysts.…”

Section: ■ Discussionmentioning

confidence: 65%

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A Conserved Second Sphere Residue Tunes Copper Site Reactivity in Lytic Polysaccharide Monooxygenases

Hall,

Joseph,

Ayuso-Fernández

et al. 2023

J. Am. Chem. Soc.

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Lytic polysaccharide monooxygenases (LPMOs) are powerful monocopper enzymes that can activate strong C–H bonds through a mechanism that remains largely unknown. Herein, we investigated the role of a conserved glutamine/glutamate in the second coordination sphere. Mutation of the Gln in NcAA9C to Glu, Asp, or Asn showed that the nature and distance of the headgroup to the copper fine-tune LPMO functionality and copper reactivity. The presence of Glu or Asp close to the copper lowered the reduction potential and decreased the ratio between the reduction and reoxidation rates by up to 500-fold. All mutants showed increased enzyme inactivation, likely due to changes in the confinement of radical intermediates, and displayed changes in a protective hole-hopping pathway. Electron paramagnetic resonance (EPR) and X-ray absorption spectroscopic (XAS) studies gave virtually identical results for all NcAA9C variants, showing that the mutations do not directly perturb the Cu(II) ligand field. DFT calculations indicated that the higher experimental reoxidation rate observed for the Glu mutant could be reconciled if this residue is protonated. Further, for the glutamic acid form, we identified a Cu(III)-hydroxide species formed in a single step on the H2O2 splitting path. This is in contrast to the Cu(II)-hydroxide and hydroxyl intermediates, which are predicted for the WT and the unprotonated glutamate variant. These results show that this second sphere residue is a crucial determinant of the catalytic functioning of the copper-binding histidine brace and provide insights that may help in understanding LPMOs and LPMO-inspired synthetic catalysts.

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Section: Discussionmentioning

confidence: 52%

Section: ■ Discussionmentioning

confidence: 65%

A Conserved Second Sphere Residue Tunes Copper Site Reactivity in Lytic Polysaccharide Monooxygenases

Hall,

Joseph,

Ayuso-Fernández

et al. 2023

J. Am. Chem. Soc.

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“…The Cu B site somewhat resembles the catalytic center of lytic polysaccharide monooxygenases (LPMOs), which hydroxylate and cleave glycosidic bonds of polysaccharides. , The LPMO active site consists of a Cu(I) ion coordinated by the side chain and amino group of an N-terminal histidine and the side chain of a second histidine, together called a histidine brace. By contrast, the Cu B site binds Cu(II) with three, not two, histidines,and differs in some details of coordination.…”

Section: Particulate Methane Monooxygenasementioning

confidence: 99%

Direct Methane Oxidation by Copper- and Iron-Dependent Methane Monooxygenases

Tucci,

Rosenzweig

2024

Chem. Rev.

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Methane is a potent greenhouse gas that contributes significantly to climate change and is primarily regulated in Nature by methanotrophic bacteria, which consume methane gas as their source of energy and carbon, first by oxidizing it to methanol. The direct oxidation of methane to methanol is a chemically difficult transformation, accomplished in methanotrophs by complex methane monooxygenase (MMO) enzyme systems. These enzymes use iron or copper metallocofactors and have been the subject of detailed investigation. While the structure, function, and active site architecture of the copper-dependent particulate methane monooxygenase (pMMO) have been investigated extensively, its putative quaternary interactions, regulation, requisite cofactors, and mechanism remain enigmatic. The iron-dependent soluble methane monooxygenase (sMMO) has been characterized biochemically, structurally, spectroscopically, and, for the most part, mechanistically. Here, we review the history of MMO research, focusing on recent developments and providing an outlook for future directions of the field. Engineered biological catalysis systems and bioinspired synthetic catalysts may continue to emerge along with a deeper understanding of the molecular mechanisms of biological methane oxidation. Harnessing the power of these enzymes will necessitate combined efforts in biochemistry, structural biology, inorganic chemistry, microbiology, computational biology, and engineering.

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“…The nature of the priming reduction separates LPMOs from other metalloenzymes that also activate inactive C-H bondsbut whose reaction cycle otherwise shows similarities to the LPMOs' catalytic cycle: 36 the iron-heme enzyme cytochrome P450 usually forms a highly oxidizing species (Cpd1) from O 2 . The resting state Fe(III)-heme unit is first reduced after substrate binding, 37,38 and O 2 binds to this Fe(II)-heme unit (similar to the O 2 pathway with reactions (3b) and (4b) in Fig.…”

Section: Introductionmentioning

confidence: 99%