The Stacking Tryptophan of Galactose Oxidase:  A Second-Coordination Sphere Residue that Has Profound Effects on Tyrosyl Radical Behavior and Enzyme Catalysis<sup>,</sup>

Rogers, Melanie S.; Tyler, Ejan M.; Akyumani, N.; Kurtis, Christian R.; Spooner, R.K.; Deacon, Sarah E.; Tamber, Sandeep; Firbank, S.J.; Mahmoud, Khaled; Knowles, Peter F.; Phillips, Simon E. V.; McPherson, Michael J.; Dooley, David M.

doi:10.1021/bi062139d

Cited by 96 publications

(83 citation statements)

References 78 publications

(144 reference statements)

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“…Delocalization of the tyrosyl radical onto the thioether bridge, which is predicted by density functional theory (DFT) computations (7,8) and EPR studies of copper-free GO (9), is postulated to contribute to the energetic stabilization of GO oxy . This postulate is consistent with the in-plane conformation of the cysteine-tyrosine cross-link observed in all known crystal structures of GO (3)(4)(5), yet the extent of hole delocalization on sulfur and consequent energetic influence in copper-bonded phenoxyls including GO oxy remain unknown (9,10).…”

supporting

confidence: 82%

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Sulfanyl stabilization of copper-bonded phenoxyls in model complexes and galactose oxidase

Verma

Pratt

Storr

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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Integrating sulfanyl substituents into copper-bonded phenoxyls significantly alters their optical and redox properties and provides insight into the influence of cysteine modification of the tyrosine cofactor in the enzyme galactose oxidase. The model complexes ½1 SR2 þ are class II mixed-valent Cu II -phenoxyl-phenolate species that exhibit intervalence charge transfer bands and intense visible sulfur-aryl π → π Ã transitions in the energy range, which provides a greater spectroscopic fidelity to oxidized galactose oxidase than non-sulfur-bearing analogs. The potentials for phenolate-based oxidations of the sulfanyl-substituted 1 SR2 are lower than the alkylsubstituted analogs by up to ca. 150 mV and decrease following the steric trend: −S t Bu > −S i Pr > −SMe. Density functional theory calculations suggest that reducing the steric demands of the sulfanyl substituent accommodates an in-plane conformation of the alkylsulfanyl group with the aromatic ring, which stabilizes the phenoxyl hole by ca. 8 kcal mol −1 (1 kcal ¼ 4.18 kJ; 350 mV) through delocalization onto the sulfur atom. Sulfur K-edge X-ray absorption spectroscopy clearly indicates a contribution of ca. 8-13% to the hole from the sulfur atoms in ½1 SR2 þ . The electrochemical results for the model complexes corroborate the ca. 350 mV (density functional theory) contribution of hole delocalization on to the cysteine-tyrosine cross-link to the stability of the phenoxyl radical in the enzyme, while highlighting the importance of the in-plane conformation observed in all crystal structures of the enzyme.Marcus-Hush analysis | density functional theory reduction potentials | noninnocent ligands | magnetic coupling G alactose oxidase (GO) is an enzyme that selectively oxidizes primary alcohols to aldehydes via a unique Cu II -tyrosyl radical with concomitant reduction of dioxygen to hydrogen peroxide (1, 2). The active site of GO contains a Cu center ligated by two histidines, one unmodified tyrosine (axial) and one tyrosine residue (equatorial) that is covalently cross-linked to a cysteine residue in a posttranslational oxidative modification step (3-5) (Fig. 1). The consensus mechanism involves two catalytically relevant forms: the reduced (GO red ), which contains a Cu I -tyrosine unit, and the oxidized (GO oxy ), which contains a Cu II center and a cysteine-modified tyrosyl radical. One-electron reduction of GO oxy generates the inactive semireduced (GO semi ) form, which contains a Cu II -tyrosinate unit. Cysteine-modification of the redox-active tyrosine significantly influences the redox properties of the active oxidant: The potential of the Tyr-Cys/Tyr•-Cys couple estimated from the GO semi ∕ GO oxy interconversion is ca. 400 mV [vs. normal hydrogen electrode (NHE), pH 7.5], which is significantly lower than free tyrosine in solution (ca. 900 mV) and unmodified redox-active tyrosines in other enzymes (ca. 660-1,000 mV) (1, 6). Delocalization of the tyrosyl radical onto the thioether bridge, which is predicted by density functional theory (DFT) compu...

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confidence: 82%

“…The active site of GO contains a Cu center ligated by two histidines, one unmodified tyrosine (axial) and one tyrosine residue (equatorial) that is covalently cross-linked to a cysteine residue in a posttranslational oxidative modification step (3)(4)(5) (Fig. 1).…”

mentioning

confidence: 99%

Sulfanyl stabilization of copper-bonded phenoxyls in model complexes and galactose oxidase

Verma

Pratt

Storr

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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“…A class I ribonucleotide reductase produces sequential radicals of multiple tyrosine groups with Mn(IV) or Fe(IV) ions 58 and oxidizes cysteine residues, generating a sulfhydryl radical 59 to reduce deoxyribonucleotides to ribonucleotides. Galactose oxidase converts primary alcohols to aldehydes via a tyrosyl radical (Y) generated by a Cu(II) ion 60,61 with the reduction of oxygen to hydrogen peroxide 62 .…”

Section: Resultsmentioning

confidence: 99%

Tyrosine-mediated two-dimensional peptide assembly and its role as a bio-inspired catalytic scaffold

et al. 2014

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In two-dimensional interfacial assemblies, there is an interplay between molecular ordering and interface geometry, which determines the final morphology and order of entire systems. Here we present the interfacial phenomenon of spontaneous facet formation in a water droplet driven by designed peptide assembly. The identified peptides can flatten the rounded top of a hemispherical droplet into a plane by forming a macroscopic two-dimensional crystal structure. Such ordering is driven by the folding geometry of the peptide, interactions of tyrosine and crosslinked stabilization by cysteine. We discover the key sequence motifs and folding structures and study their sequence-specific assembly. The well-ordered, densely packed, redox-active tyrosine units in the YYACAYY (H-Tyr-Tyr-Ala-Cys-Ala-Tyr-Tyr-OH) film can trigger or enhance chemical/electrochemical reactions, and can potentially serve as a platform to fabricate a molecularly tunable, self-repairable, flat peptide or hybrid film.

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“…12450 (40) 4157 (7) 8836 (3) 27(3) C (12) 10580 ( (19) 9130 (30) 5949 (7) 6745 (3) 17(1) C (20) 9520 (30) 6272 (7) 6448 (3) 17(1) C (21) 7910 (30) 6882 (6) 6348 (3) 17(1) C (22) 5800 (30) 7164 (7) 6540 (3) 17(1) C (23) 5440 (30) 6834 (7) 6839 (3) 17(1) C (24) 4070 (30) 6509 (7) 7336 (3) 17(1) C (25) 3590 (20) 6244 (6) 7883 (3) 14(2) C (26) 2010 (20) 6358 (6) 8193 (3) 14(2) C (27) 3750 (30) 6328 (7) 8495(3) 20(3) C (28) 2060 (30) 6377 (7) 8805 (3) 18(3) C (29) 3810 (30) 6332 (8) 9109 (3) 23(3) C (30) 2150 (40) 6415 (7) 9422(3) 24(3) C (31) 3930 …”

Section: Uj3 Ul2unclassified

“…Superoxide dismutase catalyzes the conversion of superoxide into hydrogen peroxide and oxygen [14,[18][19][20][21][22][23][24][25]. Without the action of superoxide dismutase and a cascade of enzymes, the build up of superoxide, generated during the production of ATP, leads to oxidative stress.…”

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confidence: 99%

Rational design, synthesis and characterization of amide functionalized pyridine and benzimidazole transition metal complexes.

Asem¹

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Rational design, synthesis and characterization of amide functionalized pyridine and benzimidazole transition metal complexes. This study expands our efforts to make a new class of Pt (II) compounds analogous to cisplatin and its derivatives using sterically hindered ligands. Pt compounds in this series have been synthesized using specially designed pyridine and benzimidazole ligands. These heterocycles, amide functionalized at position 2 with aryl and alkyl pendants, rapidly change their mode of coordination depending on the pH of the medium. These ligands, synthesized using condensation chemistry, also coordinate to Co(II), These complexes have been characterized using physical methods that include X-ray crystallography, IH &13C NMR, Mass spectrometry, UV and IR spectroscopies.Complexes similar in structure to cisplatin and carboplatin show varying cytotoxic properties toward different cancer cell lines. Additionally, some of these new Pt complexes show comparable and promising cytotoxicity against prostate cancer cell lines.VI

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The Stacking Tryptophan of Galactose Oxidase: A Second-Coordination Sphere Residue that Has Profound Effects on Tyrosyl Radical Behavior and Enzyme Catalysis^,

Cited by 96 publications

References 78 publications

Sulfanyl stabilization of copper-bonded phenoxyls in model complexes and galactose oxidase

Sulfanyl stabilization of copper-bonded phenoxyls in model complexes and galactose oxidase

Tyrosine-mediated two-dimensional peptide assembly and its role as a bio-inspired catalytic scaffold

Rational design, synthesis and characterization of amide functionalized pyridine and benzimidazole transition metal complexes.

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The Stacking Tryptophan of Galactose Oxidase: A Second-Coordination Sphere Residue that Has Profound Effects on Tyrosyl Radical Behavior and Enzyme Catalysis,

Cited by 96 publications

References 78 publications

Sulfanyl stabilization of copper-bonded phenoxyls in model complexes and galactose oxidase

Sulfanyl stabilization of copper-bonded phenoxyls in model complexes and galactose oxidase

Tyrosine-mediated two-dimensional peptide assembly and its role as a bio-inspired catalytic scaffold

Rational design, synthesis and characterization of amide functionalized pyridine and benzimidazole transition metal complexes.

Contact Info

Product

Resources

About

The Stacking Tryptophan of Galactose Oxidase: A Second-Coordination Sphere Residue that Has Profound Effects on Tyrosyl Radical Behavior and Enzyme Catalysis^,