Romão, MJ, Coelho C, Santos-Silva T, Foti A, Terao M, Garattini E, Leimkühler S.
2017.
Structural basis for the role of mammalian aldehyde oxidases in the metabolism of drugs and xenobiotics. Current Opinion in Chemical Biology. 37:39-47.
AbstractAldehyde oxidases (AOXs) are molybdo-flavoenzymes characterized by broad substrate specificity, oxidizing aromatic/aliphatic aldehydes into the corresponding carboxylic acids and hydroxylating various heteroaromatic rings. Mammals are characterized by a complement of species-specific \{AOX\} isoenzymes, that varies from one in humans (AOX1) to four in rodents (AOX1, AOX2, \{AOX3\} and AOX4). The physiological function of mammalian \{AOX\} isoenzymes is unknown, although human \{AOX1\} is an emerging enzyme in phase-I drug metabolism. Indeed, the number of therapeutic molecules under development which act as \{AOX\} substrates is increasing. The recent crystallization and structure determination of human \{AOX1\} as well as mouse \{AOX3\} has brought new insights into the mechanisms underlying substrate/inhibitor binding as well as the catalytic activity of this class of enzymes.
Palma, AS, Pinheiro B, Liu Y, Takeda Y, Chai W, Ito Y, Romao MJ, Carvalho AL, Feizi T.
2013.
The Structural Basis of the Recognition of Di-glucosylated N-glycans by the ER Lectin Malectin. Glycobiology. 23:1368-1369., Number 11
Abstractn/a
Bras, JLA, Cartmell A, Carvalho ALM, Verze G, Bayer EA, Vazana Y, Correia MAS, Prates JAM, Ratnaparkhe S, Boraston AB, Romao MJ, Fontes CMGA, Gilbert HJ.
2011.
Structural insights into a unique cellulase fold and mechanism of cellulose hydrolysis. Proceedings of the National Academy of Sciences of the United States of America. 108:5237-5242., Number 13
Abstractn/a
Terao, M, Romão MJ, Leimkühler S, Bolis M, Fratelli M, Coelho C, Santos-Silva T, Garattini E.
2016.
Structure and function of mammalian aldehyde oxidases. Archives of Toxicology. 90:753–780., Number 4
AbstractMammalian aldehyde oxidases (AOXs; EC1.2.3.1) are a group of conserved proteins belonging to the family of molybdo-flavoenzymes along with the structurally related xanthine dehydrogenase enzyme. AOXs are characterized by broad substrate specificity, oxidizing not only aromatic and aliphatic aldehydes into the corresponding carboxylic acids, but also hydroxylating a series of heteroaromatic rings. The number of AOX isoenzymes expressed in different vertebrate species is variable. The two extremes are represented by humans, which express a single enzyme (AOX1) in many organs and mice or rats which are characterized by tissue-specific expression of four isoforms (AOX1, AOX2, AOX3, and AOX4). In vertebrates each AOX isoenzyme is the product of a distinct gene consisting of 35 highly conserved exons. The extant species-specific complement of AOX isoenzymes is the result of a complex evolutionary process consisting of a first phase characterized by a series of asynchronous gene duplications and a second phase where the pseudogenization and gene deletion events prevail. In the last few years remarkable advances in the elucidation of the structural characteristics and the catalytic mechanisms of mammalian AOXs have been made thanks to the successful crystallization of human AOX1 and mouse AOX3. Much less is known about the physiological function and physiological substrates of human AOX1 and other mammalian AOX isoenzymes, although the importance of these proteins in xenobiotic metabolism is fairly well established and their relevance in drug development is increasing. This review article provides an overview and a discussion of the current knowledge on mammalian AOX.
Branco, PS, Peixoto D, Figueiredo M, Malta G, Roma-Rodrigues C, Batista PV, Fernandes AR, Barroso S, Carvalho AL, Afonso CAM, Ferreira LM.
2018.
Synthesis, cytotoxicity evaluation in human cell lines and in vitro DNA interaction of a hetero arylidene-9(10H)-anthrone. European Journal of Organic Chemistry. :n/a–n/a.
AbstractA new and never yet reported hetero arylidene-9(10H)-anthrone structure (4) was unexpectedly isolated on reaction of 1,2-dimethyl-3-ethylimidazolium iodide (2) and 9-anthracenecarboxaldehyde (3) under basic conditions. Its structure was unequivocally attributed by X-ray crystallography. No cytotoxicity in human healthy fibroblasts and in two different cancer cell lines was observed indicating its applicability in biological systems. Compound 4 interacts with CT-DNA by intercalation between the adjacent base pairs of DNA with a high binding affinity (Kb = 2.0(± 0.20) x 105 M-1) which is 10x higher than that described for doxorubicin (Kb = 3.2 (±0.23) × 104 M-1). Furthermore, compound 4 quenches the fluorescence emission of GelRed-CT-DNA system with a quenching constant (KSV) of 3.3(±0.3) x 103 M-1 calculated by the Stern-Volmer equation.