Macrocyclic copper(II) complexes: Superoxide scavenging activity, structural studies and cytotoxicity evaluation

Fernandes, Ana Sofia; Gaspar, Jorge; Cabral, M. Fátima; Caneiras, Cátia; Guedes, Rita C.; Rueff, José; Castro, Matilde; Costa, Judite; Oliveira, Nuno G.

doi:10.1016/j.jinorgbio.2007.01.013

Cited by 62 publications

(39 citation statements)

References 57 publications

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“…The MCOs found in many bacterial copper detoxification systems (28,42,43) have both methionine-rich sequences and cuprous oxidase activity. We have shown that Cu(I) binds to at least two sites along the CueO methionine-rich sequence near the sCu site, and these binding sites are specific for the cuprous ion; no metal binding was found at the sCu, Cu6, and Cu7 sites in crystals of C500S CueO soaked with Cu(II).…”

Section: Discussionmentioning

confidence: 99%

Crystal Structures of Multicopper Oxidase CueO Bound to Copper(I) and Silver(I)

Singh

Roberts

McDevitt

et al. 2011

Journal of Biological Chemistry

114

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Background:The multicopper oxidase CueO allows Escherichia coli to survive in aqueous solutions with a high copper concentration. Results: Cu(I) and Ag(I) ions coordinate to a flexible, methionine-rich sequence. Conclusion:The methionine-rich insert and a substrate-binding site ensure that only Cu(I) is oxidized. Significance: Understanding how bacteria survive in the presence of normally toxic concentrations of metal ions may lead to better antibacterial agents.

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Section: Discussionmentioning

confidence: 99%

Crystal Structures of Multicopper Oxidase CueO Bound to Copper(I) and Silver(I)

Singh

Roberts

McDevitt

et al. 2011

Journal of Biological Chemistry

114

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“…The MCOs found in many bacterial copper-detoxification systems have both methionine-rich structural motifs and copper(I) oxidase activity (Cha & Cooksey, 1991;Lee, Grass et al, 2002;Fernandes et al, 2007). Interestingly, a 16-residue methionine-rich -hairpin motif (Ala292-Gln307; Fig.…”

Section: Methionine-rich B-hairpin Motifmentioning

confidence: 99%

X-ray-induced catalytic active-site reduction of a multicopper oxidase: structural insights into the proton-relay mechanism and O₂-reduction states

Serrano‐Posada

Centeno-Leija

Rojas-Trejo

et al. 2015

Acta Crystallogr D Biol Crystallogr

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PDB references: Tth-MCO, 2xu9; apo Tth-MCO, 2xuw; Hg-Tth-MCO, 2xvb; Hg-Tth-MCO-2h, 4ai7; Tth-MCO-C1, 2yae; Tth-MCO-C2, 2yaf; Tth-MCO-C3, 2yah; Tth-MCO-C4, 2yam; Tth-MCO-C5, 2yao; Tth-MCO-C6, 2yap; Tth-MCO-C7, 2yaq; Tth-MCO-C8, 2yar During X-ray data collection from a multicopper oxidase (MCO) crystal, electrons and protons are mainly released into the system by the radiolysis of water molecules, leading to the X-ray-induced reduction of O 2 to 2H 2 O at the trinuclear copper cluster (TNC) of the enzyme. In this work, 12 crystallographic structures of Thermus thermophilus HB27 multicopper oxidase (Tth-MCO) in holo, apo and Hg-bound forms and with different X-ray absorbed doses have been determined. In holo Tth-MCO structures with four Cu atoms, the protondonor residue Glu451 involved in O 2 reduction was found in a double conformation: Glu451a ($7 Å from the TNC) and Glu451b ($4.5 Å from the TNC). A positive peak of electron density above 3.5 in an F o À F c map for Glu451a O "2 indicates the presence of a carboxyl functional group at the side chain, while its significant absence in Glu451b strongly suggests a carboxylate functional group. In contrast, for apo Tth-MCO and in Hg-bound structures neither the positive peak nor double conformations were observed. Together, these observations provide the first structural evidence for a proton-relay mechanism in the MCO family and also support previous studies indicating that Asp106 does not provide protons for this mechanism. In addition, eight composite structures (Tth-MCO-C1-8) with different X-ray-absorbed doses allowed the observation of different O 2 -reduction states, and a total depletion of T2Cu at doses higher than 0.2 MGy showed the high susceptibility of this Cu atom to radiation damage, highlighting the importance of taking radiation effects into account in biochemical interpretations of an MCO structure.

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“…The production of uric acid can thus be monitored by UV spectrophotometry. The protocol used to evaluate the activity of XO was adapted from Fernandes et al (19). The reaction system (final volume = 1 mL) was composed of xanthine (0.25 mM) and the sample under study, in sodium phosphate buffer 0.1 M, pH 7.8.…”

Section: Xanthine Oxidase Inhibition Assaymentioning

confidence: 99%

“…A produção de ácido úrico pode assim ser monitorizada por espectrofotometria UV. O protocolo utilizado para avaliar a atividade da XO foi adaptado de Fernandes et al (19). O sistema reacional (volume final = 1 mL) foi constituído por xantina (0,25 mM) e a amostra em estudo, em tampão fosfato de sódio 0,1 M a pH 7,8.…”

Section: Ensaio De Inibição Da Xantina Oxidaseunclassified

Xanthine Oxidase Inhibitory Activity of a Plectranthus saccatus aqueous extract

Caldeira

Costa

Rijo

et al. 2016

BBR

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Biopharmaceutical Sciences│Ciências BiofarmacêuticasBiomed Biopharm Res. , 2016; (13) 2: , 259-269 259 Biomedical and Biopharmaceutical Research J o r n a l d e I n v e s t i g a ç ã o B i o m é d i c a e B i o f a r m a c ê u t i c a Xanthine Oxidase Inhibitory Activity of a Plectranthus saccatus aqueous extract AbstractGout is a disease with high prevalence in developed countries, resulting from the deposition of uric acid crystals in various locations, particularly at the joints. The pharmacotherapeutic approach to chronic gout essentially consists of administration of uric acid-lowering agents. The main mechanism of action of these agents is the inhibition of xanthine oxidase (XO), the enzyme responsible for the formation of uric acid. The therapeutic alternatives available for this purpose are limited, thus justifying the interest of the discovery of potential new uric acidlowering drugs. In this regard, an aqueous extract of the plant Plectranthus saccatus has been studied for its ability to inhibit XO. The composition of the extract was determined by HPLC and rosmarinic acid was identified as the major constituent. Both the extract and rosmarinic acid have demonstrated the ability to inhibit the production of uric acid by interfering with XO activity. The results obtained herein support the continuation of the study of their uric acid-lowering properties in cell-based and in vivo models to further explore their potential in gout therapy. Key-words: Plectranthus saccatus, rosmarinic acid, xanthine oxidase, uric acid, gout ResumoA gota é uma patologia com elevada prevalência nos países desenvolvidos, que resulta da deposição de cristais de ácido úrico em várias localizações, sobretudo ao nível das articulações. A abordagem farmacoterapêutica da gota crónica consiste essencialmente na administração de agentes hipouricemiantes, i.e., fármacos que permitem reduzir os níveis séricos de ácido úrico. Estes agentes apresentam como principal mecanismo de ação a inibição da xantina oxidase (XO), a enzima responsável pela formação de ácido úrico. As alternativas terapêuticas disponíveis para este fim são limitadas, o que justifica o interesse da descoberta de potenciais novos fármacos hipouricemiantes. Neste âmbito, foi estudado um extrato aquoso da planta Plectranthus saccatus, relativamente à capacidade de inibição da XO. A composição do extrato foi determinada por HPLC, tendo-se identificado o ácido rosmarínico como constituinte maioritário. Tanto o extrato como o ácido rosmarínico demonstraram a capacidade de inibir a produção de ácido úrico por interferirem com a atividade da XO. Os resultados obtidos sustentam a continuação do estudo das suas propriedades hipouricemiantes em modelos celulares e in vivo, de modo a explorar mais aprofundadamente as suas potencialidades na terapêutica da gota. Palavras-chave:Plectranthus saccatus, ácido rosmarínico, xantina oxidase, ácido úrico, gota

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Macrocyclic copper(II) complexes: Superoxide scavenging activity, structural studies and cytotoxicity evaluation

Cited by 62 publications

References 57 publications

Crystal Structures of Multicopper Oxidase CueO Bound to Copper(I) and Silver(I)

Crystal Structures of Multicopper Oxidase CueO Bound to Copper(I) and Silver(I)

X-ray-induced catalytic active-site reduction of a multicopper oxidase: structural insights into the proton-relay mechanism and O₂-reduction states

Xanthine Oxidase Inhibitory Activity of a Plectranthus saccatus aqueous extract

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Macrocyclic copper(II) complexes: Superoxide scavenging activity, structural studies and cytotoxicity evaluation

Cited by 62 publications

References 57 publications

Crystal Structures of Multicopper Oxidase CueO Bound to Copper(I) and Silver(I)

Crystal Structures of Multicopper Oxidase CueO Bound to Copper(I) and Silver(I)

X-ray-induced catalytic active-site reduction of a multicopper oxidase: structural insights into the proton-relay mechanism and O2-reduction states

Xanthine Oxidase Inhibitory Activity of a Plectranthus saccatus aqueous extract

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X-ray-induced catalytic active-site reduction of a multicopper oxidase: structural insights into the proton-relay mechanism and O₂-reduction states