Amino acid sequences amine oxidases

Diamine oxidase occurs, like amine oxidase, in bacteria, animals, and plants [133]. The comparison of amino acid sequences of the amiloride-binding protein from human kidney, rat colon, diamine oxidase from human placenta, pig kidney, and amine oxidase from Hansenula polymorpha and lentil seeds has shown that the amiloride-binding protein and diamine oxidase are identical proteins[29]. The amiloride-binding protein was previously postulated to function as an epithelial sodium-transporter. While its physiological function is still... 

A phylogenetic relationship may be assumed for amine oxidase and diamine oxidase which shows distinct sequence homologies in their C-terminal regions [128]. Lysyl oxidase is not related to the other amine oxidases as it does not share any homology in structure or amino acid sequence [128] with the other amine oxidases. Non-copper enzymes with similar structures or sequences have not yet been found for any of the three enzymes. 

With few exceptions [12,27], copper amine oxidases are homodimers in the native conformation. The molecular mass of the single subunit lies in the range 70-100 kDa. Most of the eukaryotic copper amine oxidases are glycoproteins. Their isoelectric point is usually slightly below pi 7.0, but some enzymes have pi > 7.0 such as pea seedling amine oxidase [12]. The amino acid composition is known for many amine oxidases and in the last decade, the complete amino acid sequence has been determined for a number of them. Some enzymes have been prepared in a crystalline form [12], four of them have been analyzed by X-ray diffraction with complete resolution of their three dimensional structure including detailed spatial conformation of the active site [28-31]. 

Fig. (I). Topa quinone as a part of the cofactor consensus amino acid sequence in the active site of copper amine oxidases [4],...

Later, the presence of topa quinone was accordingly confirmed in the amine oxidases from porcine serum and kidney and pea seedling by resonance Raman spectrometry of active-site labeled peptides [48]. Comparison of amino acid sequences of these peptides with the sequences of those from bovine plasma and H. polymorpha amine oxidases demonstrated the presence of a consensus sequence Asp-TPQ-Asp/Glu as shown in Fig. (1). Using the pH-dependent shift of the absorption maximum of the enzyme p-nitrophenylhydrazone, which is considered to be a reliable indirect proof, the presence of topa quinone was also shown... 

In the amine oxidase from Escherichia coli, the topa quinone was confirmed by a detailed analysis of the cofactor dipeptide X-Asp [67] and the resonance Raman spectrometry of the enzyme and its derivatives[68,69]. The primary structure of the enzyme also contains the cofactor consensus sequence [70]. More bacterial genes were shown to encode proteins containing the topa quinone consensus sequence, such as amine oxidase from Klebsiella aerogenes [71], phenethylamine oxidase and histamine oxidase from Arthrobacter globiformis [72,73], and methylamine oxidase from Arthrobacter strain PI [74]. Amino acid sequences around the position of the cofactor for selected amine oxidases from various sources are given in Table 1. 

Table 1. Alignment of amino acid sequences of several copper amine oxidase around the position of topa quinone. The sequences were obtained by translation the corresponding cDNAs except for the enzymes from porcine kidney and porcine serum and the benzylamine oxidase from Hansenula polymorpha where they were determined by automated Edman degradation of peptides. Homologous consensus sequence around the cofactor is underlined, the tyrosyl precursor of topa quinone is shown as y.

Source of amine oxidase Amino acid sequence Reference... 

Formation of TPQ in the amine oxidases in which it occurs is initiated by binding of Cu to the precursor protein at the same site in which it functions as cofactor in the mature enzyme. Subsequently, the specific tyrosyl residue, the second amino acid in the conserved sequence Asn-Tyr-(Asp/Glu)-Tyr [44], is converted into TPQ in several steps, with the Cu catalyzing the oxidation of the precursor by 02 [45], Indications exist that this autocatalytic process is sometimes suboptimal most probably the insufficient availability of Cu and/or 02 in the posttranslational process is responsible [46],... 

The crystal structure of amine oxidase from Escherichia coli reveals that the C-terminal domain (440 amino acids) primarily has a /3-sandwich structure. This domain contains the active site with a type 2 copper center, the cofactor, and the dimerization contact site. Furthermore, there are three domains of approximately 100 amino acids length which have an a- and a /3-structure. The second and third of these smaller domains show marked sequence homology and are conserved in the amine oxidases of various organisms. The first of these smaller domains may, however, be lacking in some amine oxidases [28]. The structure of an eukariotic aminoxidase from pea seedling is seen in [121]. 

Structure of the active center. The active centers of this dimeric enzyme are so well embedded into its protein structure that they are inaccessible to the solvent. The two centers are situated approximately 30 A apart from each other but connected by /3-strands. The active center consists of a type 2 copper center and a cofactor. Sequence comparisons have established that the residues His 8, His 246, and His 357 coordinate the copper ions in both yeast and plants (e.g., lentil seeds) [120,122]. The participating cofactor is typical for amine oxidases, diamine oxidases, and lysyl oxidases but has not yet been found in any other protein - 2,4,5-trihydroxy-phenylalanine quinone [123, 124] (also known as TOPA-quinone, TPQ or 6-hydroxy-DOPA quinone), an internal cofactor which is created by post-translational modification of the tyrosine in position 387 [120]. The consensus sequence of the amino acids neighboring the TOPA cofactor are conserved in all known amine oxidases - Asn-TOPA-Asp/Glu [113,120, 123,125-127]. The positions of the histidine ligands relative to TOPA quinone are conserved in all known amine oxidases as well. The chain lengths of the amine oxidase monomers vary according to the organism of origin 692 residues in yeast [128], 762 in bovine serum amine oxidase [128,129] and 569 in the enzyme from lentil seeds [120,130]. 

Monoamine Oxidases (MAO) There are two MAO isoforms, MAO A and MAO B, both of which are flavoen-zymes that oxidize a wide array of neurotransmitter amines. However, they can also biotransform some xenobiotics. Both MAO isoforms consist of approximately 520 amino acid residues and share approximately 70% sequence identity. Their molecular weights are about 58K Daltons. Both isoforms are expressed in most tissues, though not necessarily in equivalent amounts. More MAO is found in liver and placenta, and least in the spleen. Actually MAO-B is... 

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