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Teixeira, S, Dias JM, Carvalho AL, Bourenkov G, Bartunik H, Almendra MJ, Moura I, Moura JJG, Romao MJ.  1999.  Crystallographic studies on a tungsten-containning formate dehydrogenase from Desulfovibrio gigas. Journal of Inorganic Biochemistry. 74:89-89., Number 1-4 AbstractWebsite
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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 AbstractWebsite

Mammalian 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.

Terao, M, Garattini E, Romão MJ, Leimkühler S.  2020.  Evolution, expression, and substrate specificities of aldehyde oxidase enzymes in eukaryotes, 2020. Journal of Biological ChemistryJournal of Biological Chemistry. 295(16):5377-5389.: Elsevier AbstractWebsite

Aldehyde oxidases (AOXs) are a small group of enzymes belonging to the larger family of molybdo-flavoenzymes, along with the well-characterized xanthine oxidoreductase. The two major types of reactions that are catalyzed by AOXs are the hydroxylation of heterocycles and the oxidation of aldehydes to their corresponding carboxylic acids. Different animal species have different complements of AOX genes. The two extremes are represented in humans and rodents; whereas the human genome contains a single active gene (AOX1), those of rodents, such as mice, are endowed with four genes (Aox1-4), clustering on the same chromosome, each encoding a functionally distinct AOX enzyme. It still remains enigmatic why some species have numerous AOX enzymes, whereas others harbor only one functional enzyme. At present, little is known about the physiological relevance of AOX enzymes in humans and their additional forms in other mammals. These enzymes are expressed in the liver and play an important role in the metabolisms of drugs and other xenobiotics. In this review, we discuss the expression, tissue-specific roles, and substrate specificities of the different mammalian AOX enzymes and highlight insights into their physiological roles.Aldehyde oxidases (AOXs) are a small group of enzymes belonging to the larger family of molybdo-flavoenzymes, along with the well-characterized xanthine oxidoreductase. The two major types of reactions that are catalyzed by AOXs are the hydroxylation of heterocycles and the oxidation of aldehydes to their corresponding carboxylic acids. Different animal species have different complements of AOX genes. The two extremes are represented in humans and rodents; whereas the human genome contains a single active gene (AOX1), those of rodents, such as mice, are endowed with four genes (Aox1-4), clustering on the same chromosome, each encoding a functionally distinct AOX enzyme. It still remains enigmatic why some species have numerous AOX enzymes, whereas others harbor only one functional enzyme. At present, little is known about the physiological relevance of AOX enzymes in humans and their additional forms in other mammals. These enzymes are expressed in the liver and play an important role in the metabolisms of drugs and other xenobiotics. In this review, we discuss the expression, tissue-specific roles, and substrate specificities of the different mammalian AOX enzymes and highlight insights into their physiological roles.

Thapper, A, Boer DR, Brondino CD, Moura JJG, Romao MJ.  2007.  Correlating EPR and X-ray structural analysis of arsenite-inhibited forms of aldehyde oxidoreductase. Journal of Biological Inorganic Chemistry. 12:353-366., Number 3 AbstractWebsite
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Thoenes, U, Flores OL, Neves A, Devreese B, Van Beeumen JJ, Huber R, Romao MJ, Legall J, Moura JJG, Rodriguespousada C.  1994.  MOLECULAR-CLONING AND SEQUENCE-ANALYSIS OF THE GENE OF THE MOLYBDENUM-CONTAINING ALDEHYDE OXIDOREDUCTASE OF DESULFOVIBRIO-GIGAS - THE DEDUCED AMINO-ACID-SEQUENCE SHOWS SIMILARITY TO XANTHINE DEHYDROGENASE. European Journal of Biochemistry. 220:901-910., Number 3 AbstractWebsite
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Trincao, J, Silva MS, Barata L, Bonifacio C, Carvalho S, Tomas AM, Ferreira AEN, Cordeiro C, Freire AP, Romao MJ.  2006.  Purification, crystallization and preliminary X-ray diffraction analysis of the glyoxalase II from Leishmania infantum. Acta Crystallographica Section F-Structural Biology and Crystallization Communications. 62:805-807. AbstractWebsite
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Trovão, F, Correia VG, Lourenço FM, Ribeiro DO, Carvalho AL, Palma AS, Pinheiro BA.  2023.  The structure of a Bacteroides thetaiotamicron carbohydrate-binding module provides new insight into the recognition of complex pectic polysaccharides by the human microbiome, 2023. :100084. AbstractWebsite

TheBacteroides thetaiotaomicronhas developed a consortium of enzymes capable of overcoming steric constraints and degrading, in a sequential manner, the complex rhamnogalacturonan II (RG-II) polysaccharide. BT0996 protein acts in the initial stages of the RGII depolymerisation, where its two catalytic modules remove the terminal monosaccharides from RG-II side chains A and B. BT0996 is modular and has three putative carbohydrate-binding modules (CBMs) for which the roles in the RG-II degradation are unknown. Here, we present the characterisation of themoduleat the C-terminal domain, which we designated BT0996C. The high-resolution structure obtained by X-ray crystallography reveals that the protein displays a typical β-sandwich fold with structural similarity to CBMs assigned to families 6 and 35. The distinctive features are: 1) the presence of several charged residues at the BT0996-C surface creating a large, broad positive lysine-rich patch that encompasses the putative binding site; and 2) the absence of the highly conserved binding-site signatures observed in CBMs from families 6 and 35, such as region A tryptophan and region C asparagine. These findings hint at a binding mode of BT0996-C not yet observed in its homologues. In line with this, carbohydrate microarrays and microscale thermophoresis show the ability of BT0996-C to bind α1-4-linked polygalacturonic acid, and that electrostatic interactions are essential for the recognition of the anionic polysaccharide. The results support the hypothesis that BT0996-C may have evolved to potentiate the action of BT0996 catalytic modules on the complex structure of RG-II by binding to the polygalacturonic acid backbone sequence.