Homemade cofactors: Self-processing in galactose oxidase

Xie, Lili; Donk, Wilfred A. van der

doi:10.1073/pnas.231485998

Cited by 22 publications

(8 citation statements)

References 37 publications

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“…In some enzymes, amino acyl groups act as covalent cofactors, e.g. in disulfide reductases [2], and in other proteins, redox cofactors are formed in situ from amino acyl groups [3], e.g. topaquinone in serum amine oxidase, tryptophan tryptophylquinone in bacterial methylamine dehydrogenase, and cysteine tryptophylquinone in bacterial quino‐cytochrome amine dehydrogenases.…”

Section: Introductionmentioning

confidence: 99%

What’s in a covalent bond?

et al. 2009

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Many enzymes use one or more cofactors, such as biotin, heme, or flavin. These cofactors may be bound to the enzyme in a noncovalent or covalent manner. Although most flavoproteins contain a noncovalently bound flavin cofactor (FMN or FAD), a large number have these cofactors covalently linked to the polypeptide chain. Most covalent flavin–protein linkages involve a single cofactor attachment via a histidyl, tyrosyl, cysteinyl or threonyl linkage. However, some flavoproteins contain a flavin that is tethered to two amino acids. In the last decade, many studies have focused on elucidating the mechanism(s) of covalent flavin incorporation (flavinylation) and the possible role(s) of covalent protein–flavin bonds. These endeavors have revealed that covalent flavinylation is a post‐translational and self‐catalytic process. This review presents an overview of the known types of covalent flavin bonds and the proposed mechanisms and roles of covalent flavinylation.

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Section: Introductionmentioning

confidence: 99%

What’s in a covalent bond?

et al. 2009

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“…TTQ is a protein-derived cofactor that is formed via the post-translational modification of two tryptophan residues in the β subunit: Trp β57 and Trp β108 in the P. denitrificans enzyme (). The existence of protein-derived cofactors has been demonstrated relatively recently, so their abundance and diversity are only just coming to light ( , ). In some cases, biogenesis is self-processing, as is seen with topaquinone (TPQ) in amine oxidases ( − ).…”

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confidence: 99%

Understanding Quinone Cofactor Biogenesis in Methylamine Dehydrogenase through Novel Cofactor Generation

et al. 2003

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Cofactors made from constitutive amino acids in proteins are now known to be relatively common. A number of these involve the generation of quinone cofactors, such as topaquinone in the copper-containing amine oxidases, and lysine tyrosylquinone in lysyl oxidase. The biogenesis of the quinone cofactor tryptophan tryptophylquinone (TTQ) in methylamine dehydrogenase (MADH) involves the post-translational modification of two constitutive Trp residues (Trp(beta)(57) and Trp(beta)(108) in Paracoccus denitrificans MADH). The modifications for generating TTQ are the addition of two oxygens to the indole ring of Trp(beta)(57) and the formation of a covalent cross-link between Cepsilon3 of Trp(beta)(57) and Cdelta1 of Trp(beta)(108). The order in which these events occur is unknown. To investigate the role Trp(beta)(108) may play in this process, this residue was mutated to both a His (betaW108H) and a Cys (betaW108C) residue. For each mutant, the majority of the protein that was isolated was inactive and exhibited weaker subunit-subunit interactions than native MADH. Analysis by mass spectrometry suggested that the inactive protein was a biosynthetic intermediate with only one oxygen atom incorporated into Trp(beta)(57) and no cross-link with residue beta108. However, in each mutant preparation, a small percentage of the mutant enzyme was active and appears to possess a functional tryptophylquinone cofactor. In the case of betaW108C, this cofactor may be identical to cysteine tryptophylquinone, recently described in the bacterial quinohemoprotein amine dehydrogenase. In betaW108H, the active cofactor is presumably a histidine tryptophylquinone, which has not been previously described, and represents the synthesis of a novel quinone protein cofactor.

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“…Broad interest has accumulated surrounding molecular, mononuclear cupric superoxide complexes due to their relevance as model systems for oxidase and oxygenase enzymes. [19][20][21][22][23][24] However, these complexes have traditionally been difficult to study due to their thermal instabilities. The earliest reports of molecular h 1 cupric superoxide complexes required the use of stopped-flow UV-vis spectroscopy under cryogenic conditions (-80 to -120 °C) in order to observe the transient 1:1 Cu:O2 species.…”

Section: Introductionmentioning

confidence: 99%

Electrosteric Stabilization of End-on Cupric Superoxide Complexes

Weberg

McCollom

Tomson

2022

Preprint

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The use of oriented internal electrostatic fields in homogenous systems is rapidly gaining attention as a nonconventional design principle for imparting unusual properties and/or reactivity profiles on metal complexes and catalysts. Herein, a series of η1 cupric superoxide complexes bound by tris(phosphinimine) ligands (X-PhMe2P3tren) are reported. Across this series of complexes, the identity of the substituent at the 4 position of a phosphinimine phenyl group was modulated (X = NMe2, H, CF3). The X-PhMe2P3tren ligands impart systematic adjustments to the electronic and secondary coordination sphere electrostatic properties of the copper complexes while maintaining a consistent steric profile in the vicinity of the O2 binding pockets. Key differences in the thermal stabilities and proton-coupled electron transfer (PCET) kinetics were observed among the η1 cupric superoxide complexes, which are discussed in the context of both intra- and inter-molecular electrostatic interactions. Notably, the cupric superoxide complex that was most resistant to decomposition – [(CF3 PhMe2P3tren)CuII(O2•1–)]+ – displays markedly improved thermal stability compared to the Me3P3tren-bound cupric superoxide complex and can be observed as high as room temperature on a multi-minute timescale. Detailed kinetic and computational analyses suggest that the improved thermal stability in this context results from an electrosteric effect, in which the accumulation of cationic charge in the secondary coordination sphere slows bimolecular decomposition.

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Homemade cofactors: Self-processing in galactose oxidase

Cited by 22 publications

References 37 publications

What’s in a covalent bond?

What’s in a covalent bond?

Understanding Quinone Cofactor Biogenesis in Methylamine Dehydrogenase through Novel Cofactor Generation

Electrosteric Stabilization of End-on Cupric Superoxide Complexes

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