Enzymatic Carbon–Sulfur Bond Formation in Natural Product Biosynthesis

Chemical Reviews, Journal Year: 2017, Volume and Issue: 117(8), P. 5521 - 5577

Published: April 18, 2017

Sulfur plays a critical role for the development and maintenance of life on earth, which is reflected by wealth primary metabolites, macromolecules, cofactors bearing this element. Whereas large body knowledge has existed sulfur trafficking in metabolism, secondary metabolism involving long been neglected. Yet, diverse functionalities have major impact biological activities natural products. Recent research at genetic, biochemical, chemical levels unearthed broad range enzymes, shuttles, mechanisms generating carbon–sulfur bonds. This Review will give first systematic overview enzymes catalyzing formation organosulfur

Language: Английский

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Structure and Function of Human Tyrosinase and Tyrosinase‐Related Proteins

Chemistry - A European Journal, Journal Year: 2017, Volume and Issue: 24(1), P. 47 - 55

Published: Oct. 20, 2017

Melanin is the main pigment responsible for color of human skin, hair and eye. Its biosynthesis requires three melanogenic enzymes, tyrosinase (TYR), tyrosinase-related proteins TYRP1 TYRP2. The difficulty isolating pure homogeneous from endogenous sources has hampered their study, resulted in many contradictory findings regarding physiological functions. In this review, we summarize recent advances on structure function TYR TYRPs by virtue crystal TYRP1, which first available a mammalian enzyme. This structure, combined with structures other lower eukaryotes mutagenesis studies key active site residues, sheds light mechanism TYRPs. Furthermore, TYRP1-based homology model provides high-quality platform to map analyze albinism-related mutations, as well design specific antimelanogenic compounds. Finally, provide perspectives future structure/function

Language: Английский

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Activation of dioxygen by copper metalloproteins and insights from model complexes

JBIC Journal of Biological Inorganic Chemistry, Journal Year: 2016, Volume and Issue: 22(2-3), P. 253 - 288

Published: Dec. 5, 2016

Language: Английский

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Inhibition of Human Tyrosinase Requires Molecular Motifs Distinctively Different from Mushroom Tyrosinase

Journal of Investigative Dermatology, Journal Year: 2018, Volume and Issue: 138(7), P. 1601 - 1608

Published: Feb. 7, 2018

Tyrosinase is the rate-limiting enzyme of melanin production and, accordingly, most prominent target for inhibiting hyperpigmentation. Numerous tyrosinase inhibitors have been identified, but those lack clinical efficacy because they were identified using mushroom as target. Therefore, we used recombinant human to screen a library 50,000 compounds and compared active screening hits with well-known whitening ingredients. Hydroquinone its derivative arbutin only weakly inhibited half-maximal inhibitory concentration (IC50) in millimolar range, kojic acid showed weak (IC50 > 500 μmol/L). The potent this resorcinyl-thiazole derivatives, especially newly Thiamidol (Beiersdorf AG, Hamburg, Germany) (isobutylamido thiazolyl resorcinol), which had an IC50 1.1 μmol/L. In contrast, = 108 melanocyte cultures, strongly reversibly 0.9 μmol/L), whereas hydroquinone irreversibly melanogenesis 16.3 Clinically, visibly reduced appearance age spots within 4 weeks, after 12 weeks some indistinguishable from normal adjacent skin. full potential reduce hyperpigmentation skin needs be explored future studies.

Language: Английский

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The pearl oyster Pinctada fucata martensii genome and multi-omic analyses provide insights into biomineralization

GigaScience, Journal Year: 2017, Volume and Issue: 6(8)

Published: July 25, 2017

Abstract Nacre, the iridescent material found in pearls and shells of molluscs, is formed through an extraordinary process matrix-assisted biomineralization. Despite recent advances, many aspects biomineralization its evolutionary origin remain unknown. The pearl oyster Pinctada fucata martensii a well-known master biomineralization, but molecular mechanisms that underlie production are not fully understood. We sequenced highly polymorphic genome conducted multi-omic biochemical studies to probe nacre formation. identified large set novel proteins participating matrix-framework formation, expanded families, including components similar vertebrate bones such as collagen-related VWA-containing proteins, chondroitin sulfotransferases, regulatory elements. Considering there only collagen-based matrices chitin-based most invertebrate skeletons, presence both chitin elements suggests chitin- have deep roots might be part ancient biomineralizing matrix. Our results expand current shell model provide new insights into evolution diverse systems.

Language: Английский

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Homogeneous Oxygenase Catalysis

Chemical Reviews, Journal Year: 2018, Volume and Issue: 118(10), P. 4912 - 4945

Published: April 9, 2018

Oxygenases-catalyzed reductive activation of molecular oxygen and incorporation O atoms into an organic molecule is undoubtedly one the most attractive research areas. Typically, these oxygenation reactions proceed with high selectivity reactivity, which seldom found in its "biomimetic" chemocatalytic counterparts. Furthermore, enzymatic can avoid undesired overoxidation, frequently observed (industrial) chemical transformation. Therefore, it not surprising that tremendous attention has been paid to oxygenation. Their application synthesis steadily growing over years. The goal present Review provide a handy reference for chemists interested using homogeneous oxygenase catalysis those discovering new types biomimetic oxidations oxygenations dioxygen. In this Review, we will review recent advances reveal great achievements potentials field.

Language: Английский

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The unravelling of the complex pattern of tyrosinase inhibition

Scientific Reports, Journal Year: 2016, Volume and Issue: 6(1)

Published: Oct. 11, 2016

Abstract Tyrosinases are responsible for melanin formation in all life domains. Tyrosinase inhibitors used the prevention of severe skin diseases, skin-whitening creams and to avoid fruit browning, however continued use many such is considered unsafe. In this study we provide conclusive evidence inhibition mechanism two well studied tyrosinase inhibitors, KA (kojic acid) HQ (hydroquinone), which extensively hyperpigmentation treatment. reported literature with contradicting mechanisms, while described as both a inhibitor substrate. By visualization active site TyrBm crystals, together molecular modeling, binding constant analysis kinetic experiments, have elucidated their mechanisms inhibition, was ambiguous inhibitors. We confirm that acts mixed inhibitor, can act substrate an inhibitor.

Language: Английский

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Five individual polyphenols as tyrosinase inhibitors: Inhibitory activity, synergistic effect, action mechanism, and molecular docking

Food Chemistry, Journal Year: 2019, Volume and Issue: 297, P. 124910 - 124910

Published: May 27, 2019

Language: Английский

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Immunological properties of oxygen-transport proteins: hemoglobin, hemocyanin and hemerythrin

Cellular and Molecular Life Sciences, Journal Year: 2016, Volume and Issue: 74(2), P. 293 - 317

Published: Aug. 12, 2016

It is now well documented that peptides with enhanced or alternative functionality (termed cryptides) can be liberated from larger, and sometimes inactive, proteins. A primary example of this phenomenon the oxygen-transport protein hemoglobin. Aside respiration, hemoglobin hemoglobin-derived have been associated immune modulation, hematopoiesis, signal transduction microbicidal activities in metazoans. Likewise, functional equivalents to invertebrates, namely hemocyanin hemerythrin, act as potent effectors under certain physiological conditions. The purpose review evaluate true extent dynamics innate immunity, impress upon reader multi-functionality these ancient proteins on basis their structures. In context, erythrocyte–pathogen antibiosis competences various erythroid cells are compared across diverse taxa.

Language: Английский

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Tyrosinase versus Catechol Oxidase: One Asparagine Makes the Difference

Angewandte Chemie International Edition, Journal Year: 2016, Volume and Issue: 55(8), P. 2884 - 2888

Published: Jan. 15, 2016

Abstract Tyrosinases mediate the ortho ‐hydroxylation and two‐electron oxidation of monophenols to ‐quinones. Catechol oxidases only catalyze diphenols. Although it is significant interest, origin functional discrimination between tyrosinases catechol has been unclear. Recently, postulated that a glutamate an asparagine bind activate conserved water molecule towards deprotonation monophenols. Here we demonstrate for first time polyphenoloxidase, which exhibits diphenolase activity, can be transformed tyrosinase by mutation introduce asparagine. The are necessary properly orient in order abstract proton from monophenol. These results provide direct evidence crucial importance shuttle activity type 3 copper proteins, allowing consistent understanding their different chemical reactivities.

Language: Английский

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