FAD-containing polyamine oxidases use secondary amines spermine and spermidine as their preferred substrates, and thereby possibly regulate cell growth ( Seiler, 1990). tyramine, adrenaline) ( Shih et al., 1999). noradrenaline) and other biogenic amines (e.g. MAO-A and -B are well known mitochondrial enzymes that have firmly established roles in the metabolism of neurotransmitters (e.g. The FAD- and TPQ-containing AOs not only differ in their cofactors, but are also distinct in terms of their subcellular distribution, substrates, inhibitors and biological functions ( Figure 1). Figure 1C is by the courtesy of Dr Tiina Salminen, Åbo Akademi University, Turku, Finland. The other highlighted residues are TPQ, Tyr372, Tyr384 and Asp386 (red). His520, His522 and His684 (blue) bind to the copper ion (yellow). The important active site residues are shown under the transparent surface. The inset shows a closer view of the active site. ( C) An overall fold of the catalytically active domain (D4) of a human SSAO (VAP-1). The line above the SSAO molecule illustrates the approximate amino acid positions of each important motif (the overall length of SSAO varies and hence the numbers are only approximations). The characteristic positions of the catalytic base, copper-coordinating histidines and the four amino acids-long sequence containing the tyrosine, which is modified to TPQ, as an SSAO sequence signature are shown. In the N-terminus either a secretion signal or a transmembrane segment is found. NA, noradrenaline DA, dopamine A, adrenaline β-PEA, β-phenylethylamine trypt, tryptamine, ECM, extracellular matrix AOC, amine oxidase, copper-dependent. These enzymes are collectively designated as SSAOs due to their characteristic sensitivity of inhibition by a carbonyl-reactive compound, semicarbazide. These enzymes include diamine oxidases, lysyl oxidase, and plasma membrane and soluble MAOs. The other class of AOs contain a cofactor possessing one or more carbonyl groups, which appears to be topa-quinone (TPQ) in most cases ( Klinman and Mu, 1994 Klinman, 1996 Lyles, 1996). The flavin adenine dinucleotide (FAD)-containing enzymes are intracellular enzymes ( Shih et al., 1999). Enzymatic classification of amine oxidasesĪmine oxidases (AOs) have been traditionally divided into two main groups, based on the chemical nature of the attached cofactor ( Figure 1A). Here we summarize some of the data that have accumulated during recent years to reveal the biological function of semicarbazide-senistive amine oxidases (SSAOs), one special class of ectoenzymes. However, these cell surface enzymes are often large glycoproteins themselves and hence can provide many protein domains and oligosaccharide moieties for other non-enzymatic recognition events as well. CD143/Angiotensin-converting enzyme is responsible for proteolytic cleavage of inactive angiotensin I to biologically active angiotensin II).
CD73/Ecto-5′ nucleotidase dephosphorylates AMP and IMP to adenosine and inosine, respectively) or by locally activating or inactivating biologically active peptides (e.g. They can also regulate cell signalling by producing or destroying nucleotides (e.g. Consequently, ectoenzymes have been implicated in uptake and recycling of nutrients and in degradation of extracellular foreign DNA. These molecules have the capacity to catalyse enzymatic reactions in the immediate vicinity of the cell surface, and thereby regulate the concentration and functions of their substrates and end products, which are often biologically active. Recently, an increasing number of enzymes are being recognized as cell surface proteins (e.g. This functional division (rather than sequence alignments) also forms the basis for the current Enzyme Commission (EC) classification ( ). Enzymes have been traditionally thought to act as catalysts in complex biochemical pathways within a cell, and they have been classified according to the nature of the enzymatic reaction they catalyse (e.g.
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