Type-2 copper-containing enzymes

Macpherson, Iain; Murphy, M.E.P.

doi:10.1007/s00018-007-7310-9

Cited by 122 publications

(91 citation statements)

References 93 publications

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“…Both marine nirK clades were represented by the sequences retrieved exclusively from epi and bathypelagic seawater, and exhibited high divergence with 'soil' and 'thermophilic' crenarchaeal and bacterial nirK clades (Figure 3). According to the predictions of MacPherson and Murphy (2007), the absence of four histidine residues at positions His 43 , His 87 , His 270 and His 321 (Achromobacter cycloclastes NirK numbering), required for trinuclear copper coordination, strongly suggests that NirK-like proteins of 'marine' lineages are NirKs and not multicopper oxidases. Such His-containing multicopper oxidase (CENSYa_1582) was initially annotated as NirK in the genome of C. symbiosum (Hallam et al, 2006a, b), the marine sponge symbiont, which is actually lacking NirK (Bartossek et al, 2010).…”

Section: Deep-sea Crenarchaeota-specific Genes Encoding Nirkmentioning

confidence: 99%

Contribution of crenarchaeal autotrophic ammonia oxidizers to the dark primary production in Tyrrhenian deep waters (Central Mediterranean Sea)

et al. 2011

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Mesophilic Crenarchaeota have recently been thought to be significant contributors to nitrogen (N) and carbon (C) cycling. In this study, we examined the vertical distribution of ammonia-oxidizing Crenarchaeota at offshore site in Southern Tyrrhenian Sea. The median value of the crenachaeal cell to amoA gene ratio was close to one suggesting that virtually all deep-sea Crenarchaeota possess the capacity to oxidize ammonia. Crenarchaea-specific genes, nirK and ureC, for nitrite reductase and urease were identified and their affiliation demonstrated the presence of 'deep-sea' clades distinct from 'shallow' representatives. Measured deep-sea dark CO 2 fixation estimates were comparable to the median value of photosynthetic biomass production calculated for this area of Tyrrhenian Sea, pointing to the significance of this process in the C cycle of aphotic marine ecosystems. To elucidate the pivotal organisms in this process, we targeted known marine crenarchaeal autotrophy-related genes, coding for acetyl-CoA carboxylase (accA) and 4-hydroxybutyryl-CoA dehydratase (4-hbd). As in case of nirK and ureC, these genes are grouped with deepsea sequences being distantly related to those retrieved from the epipelagic zone. To pair the molecular data with specific functional attributes we performed [ 14 C]HCO 3 incorporation experiments followed by analyses of radiolabeled proteins using shotgun proteomics approach. More than 100 oligopeptides were attributed to 40 marine crenarchaeal-specific proteins that are involved in 10 different metabolic processes, including autotrophy. Obtained results provided a clear proof of chemolithoautotrophic physiology of bathypelagic crenarchaeota and indicated that this numerically predominant group of microorganisms facilitate a hitherto unrecognized sink for inorganic C of a global importance.

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Section: Deep-sea Crenarchaeota-specific Genes Encoding Nirkmentioning

confidence: 99%

Contribution of crenarchaeal autotrophic ammonia oxidizers to the dark primary production in Tyrrhenian deep waters (Central Mediterranean Sea)

et al. 2011

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“…[1][2][3][4][5][6][7] It was suggested that Cu 2+ and several other dications could act as catalysts for the formation of peptide bonds in aqueous solution. 8,9 Cu 2+ can readily move across cell membranes and through ion channels and become toxic at elevated cellular concentrations.…”

Section: Introductionmentioning

confidence: 99%

Computational Study of Copper(II) Complexation and Hydrolysis in Aqueous Solutions Using Mixed Cluster/Continuum Models

2009

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We use density functional theory (B3LYP) and the COSMO continuum solvent model to characterize the structure and stability of the hydrated Cu(II) complexes [Cu(MeNH 2 2-x (x ) 1-3) as a function of metal coordination number (4-6) and cluster size (n ) 4-8, 18). The small clusters with n ) 4-8 are found to be the most stable in the nearly square-planar four-coordinate configuration,, which is three-coordinate. In the presence of the two full hydration shells (n ) 18), however, the five-coordinate square-pyramidal geometry is the most favorable for Cu (MeNH 2 ) 2+ (5, 6) and Cu(OH) + (5, 4, 6), and the four-coordinate geometry is the most stable for Cu(OH) 2 (4, 5) and Cu(OH) 3 -(4). (Other possible coordination numbers for these complexes in the aqueous phase are shown in parentheses.) A small energetic difference between these structures (0.23-2.65 kcal/mol) suggests that complexes with different coordination numbers may coexist in solution. Using two full hydration shells around the Cu 2+ ion (18 ligands) gives Gibbs free energies of aqueous reactions that are in excellent agreement with experiment. The mean unsigned error is 0.7 kcal/mol for the three consecutive hydrolysis steps of Cu 2+ and the complexation of Cu 2+ with methylamine. Conversely, calculations for the complexes with only one coordination shell (four equatorial ligands) lead to a mean unsigned error that is >6.0 kcal/mol. Thus, the explicit treatment of the first and the second shells is critical for the accurate prediction of structural and thermodynamic properties of Cu(II) species in aqueous solution.

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“…Preventing this ET to Cu II M -OOH is functionally required because it would generate Cu I -O(H)OH, which would lead to deleterious Fenton chemistry. The requirement for large λ i offers an explanation for why Nature chose the counterintuitive Cu H site for electron transfer, especially because type 2 His 3 Cu sites are generally used directly for substrate binding and oxidation/reduction in other enzymes (for example, in copper amine oxidase, nitrite reductase, and superoxide dismutase) (33). In particular, if Cu H were replaced by a type 1, blue, copper ET site (with λ i ∼0.35), premature ET leading to Fenton chemistry would be accessible with a rate approaching 0.1 s -1 (SI Appendix, Fig.…”

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confidence: 99%

Mechanism of O₂activation and substrate hydroxylation in noncoupled binuclear copper monooxygenases

Cowley

Solomon

2016

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

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Peptidylglycine α-hydroxylating monooxygenase (PHM) and dopamine β-monooxygenase (DβM) are copper-dependent enzymes that are vital for neurotransmitter regulation and hormone biosynthesis. These enzymes feature a unique active site consisting of two spatially separated (by 11 Å in PHM) and magnetically noncoupled copper centers that enables 1e -activation of O 2 for hydrogen atom abstraction (HAA) of substrate C-H bonds and subsequent hydroxylation. Although the structures of the resting enzymes are known, details of the hydroxylation mechanism and timing of long-range electron transfer (ET) are not clear. This study presents density-functional calculations of the full reaction coordinate, which demonstrate: (i) the importance of the end-on coordination of superoxide to Cu for HAA along the triplet spin surface; (ii) substrate radical rebound to a Cu II hydroperoxide favors the proximal, nonprotonated oxygen; and (iii) long-range ET can only occur at a late step with a large driving force, which serves to inhibit deleterious Fenton chemistry. The large inner-sphere reorganization energy at the ET site is used as a control mechanism to arrest premature ET and dictate the correct timing of ET. C opper is an essential cofactor for many cellular processes requisite for life (1). In particular, one or multiple coppers are found in active sites of enzymes that bind, activate, and reduce O 2 using the biologically accessible Cu II /Cu I redox couple (2, 3). One important class of Cu-dependent O 2 -activating enzymes is responsible for the stereospecific C-H α-hydroxylation of hormones and glycine-extended neuropeptides for proper neurotransmitter regulation and hormone biosynthesis. These enzymes [peptidylglycine α-hydroxylating monooxygenase (PHM), dopamine β-monooxygenase (DβM), and tyramine β-monooxygenase (TβM)] feature two distinct Cu sites (designated Cu M and Cu H ) separated in the protein by an ∼11-Å distance ( Fig. 1) (4-6). The lack of magnetic coupling between these sites distinguishes this class as "noncoupled" binuclear copper monooxygenases, in contrast to coupled binuclear copper enzymes (tyrosinase, hemocyanin, etc.). Intriguingly, a recent structure of dimeric DβM (7) shows an "open" conformation reminiscent of PHM in one apo monomer (predicted Cu-Cu distance ∼14 Å) and a "closed" conformation in the second half-apo monomer with a significantly contracted core (predicted Cu-Cu distance ∼5 Å). This suggests that the domains containing Cu H and Cu M have some conformational flexibility; however, it is currently unknown whether this is relevant to turnover. The Cu M site, featuring a 2His/1Met ligand set, is the center involved in O 2 activation, and the Cu H site, supported by 3His coordination, is an unusual electron transfer (ET) site that provides the second electron required for turnover.Kinetic isotope studies on PHM, DβM, and TβM have established several important parameters of the mechanism of C-H hydroxylation. A large intrinsic substrate H/D isotope effect (10.6) on the C-H cleavage step in PHM...

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Type-2 copper-containing enzymes

Cited by 122 publications

References 93 publications

Contribution of crenarchaeal autotrophic ammonia oxidizers to the dark primary production in Tyrrhenian deep waters (Central Mediterranean Sea)

Contribution of crenarchaeal autotrophic ammonia oxidizers to the dark primary production in Tyrrhenian deep waters (Central Mediterranean Sea)

Computational Study of Copper(II) Complexation and Hydrolysis in Aqueous Solutions Using Mixed Cluster/Continuum Models

Mechanism of O₂activation and substrate hydroxylation in noncoupled binuclear copper monooxygenases

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Type-2 copper-containing enzymes

Cited by 122 publications

References 93 publications

Contribution of crenarchaeal autotrophic ammonia oxidizers to the dark primary production in Tyrrhenian deep waters (Central Mediterranean Sea)

Contribution of crenarchaeal autotrophic ammonia oxidizers to the dark primary production in Tyrrhenian deep waters (Central Mediterranean Sea)

Computational Study of Copper(II) Complexation and Hydrolysis in Aqueous Solutions Using Mixed Cluster/Continuum Models

Mechanism of O2activation and substrate hydroxylation in noncoupled binuclear copper monooxygenases

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Mechanism of O₂activation and substrate hydroxylation in noncoupled binuclear copper monooxygenases