pH-Linked Binding of Mn(II) to Manganese Peroxidase

Mr, Mauk; Kishi, Kiyozo; Mh, Gold; Ag, Mauk

doi:10.1021/bi972932u

Cited by 21 publications

(11 citation statements)

References 19 publications

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“…Similar binding has been described for P. chrysosporium MnP (Sundaramoorthy et al, 2005), although the third site does not exist owing to the shorter C-tail. Metal binding would contribute to haem fixation on the protein, resulting in improved enzyme stability, as reported for the P. chrysosporium and D. squalens MnPs (Mauk et al, 1998;Youngs, Sundaramoorthy et al, 2000) and as confirmed here for both short and long MnPs. Moreover, Cd 2+ binding at the Mn-oxidation site enabled us to describe ABTS oxidation at the same site, as shown by competitive inhibition results.…”

Section: Structural-functional Evaluation Of the Variable Stability Psupporting

confidence: 87%

Structural implications of the C-terminal tail in the catalytic and stability properties of manganese peroxidases from ligninolytic fungi

Fernández‐Fueyo

Acebes

Ruíz-Dueñas

et al. 2014

Acta Cryst D Biol Crystallogr

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The variable C-terminal tail of manganese peroxidases, a group of enzymes involved in lignin degradation, is implicated in their catalytic and stability properties, as shown by new crystal structures, molecular-simulation and directed-mutagenesis data. Based on this structural–functional evaluation, short and long/extralong manganese peroxidase subfamilies have been accepted; the latter are characterized by exceptional stability, while it is shown for the first time that the former are able to oxidize other substrates at the same site where manganese(II) is oxidized.

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Section: Structural-functional Evaluation Of the Variable Stability Psupporting

confidence: 87%

Structural implications of the C-terminal tail in the catalytic and stability properties of manganese peroxidases from ligninolytic fungi

Fernández‐Fueyo

Acebes

Ruíz-Dueñas

et al. 2014

Acta Cryst D Biol Crystallogr

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“…This network of hydrogen bonds is possible only with the open conformation of Glu39. Although Mn II is not observed to bind at this site in the crystal structures, a second, lower-affinity Mn-binding site has been postulated on the basis of pH binding analysis of the protein in solution (48). It is possible that Mn II does bind to this site under physiological conditions, but not under the conditions for crystal formation (pH 6.5 in cacodylate buffer).…”

Section: Resultsmentioning

confidence: 98%

High-Resolution Crystal Structure of Manganese Peroxidase: Substrate and Inhibitor Complexes^,

et al. 2005

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Manganese peroxidase (MnP) is an extracellular heme enzyme that catalyzes the peroxidedependent oxidation of Mn II to Mn III . The Mn III is released from the enzyme in complex with oxalate. One heme propionate and the side chains of Glu35, Glu39, and Asp179 were identified as Mn II ligands in the 2.0 Å resolution crystal structure. The new 1.45 Å crystal structure of MnP complexed with Mn II provides a more accurate view of the Mn-binding site. New features include possible partial protonation of Glu39 in the Mn-binding site and glycosylation at Ser336. This is also the first report of MnPinhibitor complex structures. At the Mn-binding site, divalent Cd II exhibits octahedral, hexacoordinate ligation geometry similar to that of Mn II . Cd II also binds to a putative second weak metal-binding site with tetrahedral geometry at the C-terminus of the protein. Unlike that for Mn II and Cd II , coordination of trivalent Sm III at the Mn-binding site is octacoordinate. Sm III was removed from a MnP-Sm III crystal by soaking the crystal in oxalate and then reintroduced into the binding site. Thus, direct comparisons of Sm III -bound and metal-free structures were made using the same crystal. No ternary complex was observed upon incubation with oxalate. The reversible binding of Sm III may be a useful model for the reversible binding of Mn III to the enzyme, which is too unstable to allow similar examination.White-rot basidiomycetous fungi are the only organisms capable of degrading the phenylpropanoid, plant cell wall polymer, lignin (1-4). The lignin-degrading system of these fungi also can oxidize a variety of economically and environmentally important aromatic pollutants (5-9). Under ligninolytic conditions, the best-studied lignin-degrading fungus, Phanerochaete chrysosporium, secretes two families of extracellular heme peroxidases, lignin peroxidase (LiP) and manganese peroxidase (MnP) 1 (2-4, 10), and a hydrogen peroxide-generating system (2, 4, 6).MnP from P. chrysosporium has been studied extensively by a variety of biochemical and biophysical methods (11)(12)(13)(14)(15). The crystal structure illustrates that the heme environment of MnP is similar to that of other plant and fungal peroxidases (16). However, MnP is the only heme peroxidase capable of the one-electron oxidation of Mn II in a typical peroxidase reaction cycle:where MnPI and MnPII are the oxidized intermediates MnP compounds I and II, respectively. The 2.0 Å resolution crystal structure of MnP, determined at room temperature, shows that the substrate, Mn II , binds to one heme propionate and the side chains of three amino acids, Glu35, Glu39, and Asp179, as well as two solvent ligands (16) (Figure 1). This site was confirmed by kinetic and biophysical studies of wild-type MnP and of proteins containing point mutations in the putative binding site. † This research was supported by Grants GM42614 (to T.L.P.) and DK62524 (to M.S.) from the National Institutes of Health and Grants MCB-9808420 from the National Science Foundation and DE-03-9...

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“…At this pH both sites would be occupied when the protein is exposed to micromolar concentrations of manganese. Unlike other metals such as copper, affinity values for manganese binding to known manganese-binding proteins are quite low and in the micromolar range (37)(38)(39)(40)(41)(42)(43). Divalent metal transporter-1 (DMT-1) is the only known transporter for Mn 2ϩ .…”

Section: Discussionmentioning

confidence: 99%

Manganese Binding to the Prion Protein

Brazier

Davies

Player

et al. 2008

Journal of Biological Chemistry

102

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There is considerable evidence that the prion protein binds copper. However, there have also been suggestions that prion protein (PrP) binds manganese. We used isothermal titration calorimetry to identify the manganese binding sites in wild-type mouse PrP. The protein showed two manganese binding sites with affinities that would bind manganese at concentrations of 63 and 200 M at pH 5.5. This indicates that PrP binds manganese with affinity similar to other known manganese-binding proteins. Further study indicated that the main manganese binding site is associated with His-95 in the so-called "fifth site" normally associated with copper binding. Additionally, it was shown that occupancy by copper does not prevent manganese binding. Under these conditions, manganese binding resulted in an altered conformation of PrP, displacement of copper, and altered redox chemistry of the metal-protein complex. Cyclic voltammetric measurements suggested a complex redox chemistry involving manganese bound to PrP, whereas copper-bound PrP was able to undergo fully reversible electron cycling. Additionally, manganese binding to PrP converted it to a form able to catalyze aggregation of metal-free PrP. These results further support the notion that manganese binding could cause a conformation change in PrP and trigger changes in the protein similar to those associated with prion disease.

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pH-Linked Binding of Mn(II) to Manganese Peroxidase

Cited by 21 publications

References 19 publications

Structural implications of the C-terminal tail in the catalytic and stability properties of manganese peroxidases from ligninolytic fungi

Structural implications of the C-terminal tail in the catalytic and stability properties of manganese peroxidases from ligninolytic fungi

High-Resolution Crystal Structure of Manganese Peroxidase: Substrate and Inhibitor Complexes^,

Manganese Binding to the Prion Protein

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pH-Linked Binding of Mn(II) to Manganese Peroxidase

Cited by 21 publications

References 19 publications

Structural implications of the C-terminal tail in the catalytic and stability properties of manganese peroxidases from ligninolytic fungi

Structural implications of the C-terminal tail in the catalytic and stability properties of manganese peroxidases from ligninolytic fungi

High-Resolution Crystal Structure of Manganese Peroxidase: Substrate and Inhibitor Complexes,

Manganese Binding to the Prion Protein

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High-Resolution Crystal Structure of Manganese Peroxidase: Substrate and Inhibitor Complexes^,