This domain can be found in NAD(P)H-flavin oxidoreductases (flavin reductases), a class of enzymes capable of producing reduced flavin for bacterial bioluminescence and other biological processes, and various other oxidoreductase and monooxygenase enzymes [, , ].This domain consists of a β-barrel with Greek key topology, and is related to the ferredoxin reductase-like FAD-binding domain. The flavin reductases have a different dimerisation mode than that found in the PNP oxidase-like family, which also carries an FMN-binding domain with a similar topology.
The following phosphorylases are in the same family:Purine nucleoside phosphorylase () (PNP) from most bacteria (gene deoD), which catalyses the cleavage of guanosine or inosine to respective bases and sugar-1-phosphate molecules [].Uridine phosphorylase () (UdRPase) from bacteria (gene udp) and mammals, which catalyses the cleavage of uridine into uracil and ribose-1-phosphate, the products of the reaction are used either as carbon and energy sources or in the rescue of pyrimidine bases for nucleotide synthesis [].5'-methylthioadenosine phosphorylase () (MTA phosphorylase) from Sulfolobus solfataricus [].It should be noted that mammalian and some bacterial PNP as well as eukaryotic MTA phosphorylase belong to a different family of phosphorylases.
This entry represents the DEXQ-box helicase domain found in Suv3 and related proteins. Suv3 is an NTP-dependent RNA/DNA helicase that is necessary for the degradation of mature mtRNAs. It localizes predominantly in the mitochondria, where it forms an RNA-degrading complex called mitochondrial degradosome (mtEXO) with exonuclease PNP (polynucleotide phosphorylase), that degrades 3' overhang double-stranded RNA with a 3'-to-5' directionality in an ATP-dependent manner. Suv3 plays a role in the RNA surveillance system in mitochondria; it regulates the stability of mature mRNAs, the removal of aberrantly formed mRNAs and the rapid degradation of non coding processing intermediates []. It also confers salinity and drought stress tolerance by maintaining both photosynthesis and antioxidant machinery, probably via an increase in plant hormone levels such as gibberellic acid (GA3), the cytokinin zeatin (Z), and indole-3-acetic acid (IAA) [, ].Proteins containing this domain also include some bacterial RNA helicases.
Pyridoxal phosphate is the active form of vitamin B6 (pyridoxine or pyridoxal). Pyridoxal 5'-phosphate (PLP) is a versatile catalyst, acting as a coenzyme in a multitude of reactions, including decarboxylation, deamination and transamination [, , ]. PLP-dependent enzymes are primarily involved in the biosynthesis of amino acids and amino acid-derived metabolites, but they are also found in the biosynthetic pathways of amino sugars and in the synthesis or catabolism of neurotransmitters; pyridoxal phosphate can also inhibit DNA polymerases and several steroid receptors []. Inadequate levels of pyridoxal phosphate in the brain can cause neurological dysfunction, particularly epilepsy [].PLP enzymes exist in their resting state as a Schiff base, the aldehyde group of PLP forming a linkage with the ε-amino group of an active site lysine residue on the enzyme. The α-amino group of the substrate displaces the lysine ε-amino group, in the process forming a new aldimine with the substrate. This aldimine is the common central intermediate for all PLP-catalysed reactions, enzymatic and non-enzymatic [].In Escherichia coli, the pdx genes involved in vitamin B6 have been characterised [, , ]. This entry represents PdxJ (also called PNP synthase), which catalyses the condensation of 4-hydroxy-L-threonine and 1-deoxy-D-xylulose-5-phosphate to form pyridoxine-5'-phosphate (PNP) []. The product of the PdxJ reaction is then oxidized by PdxH to form pyridoxal 5'-phosphate (PLP).PNP synthase (PdxJ) adopts a TIM barrel topology. Intersubunit contacts are mediated by three ''extra'' helices, generating a tetramer of symmetric dimers with shared active sites. The open state has been proposed to accept substrates and to release products, while most of the catalytic events are likely to occur in the closed state. A hydrophilic channel running through the centre of the barrel was identified as the essential structural feature that enables PNP synthase to release water molecules produced during the reaction from the closed, solvent-shielded active site [].
Pyridoxal phosphate is the active form of vitamin B6 (pyridoxine or pyridoxal). Pyridoxal 5'-phosphate (PLP) is a versatile catalyst, acting as a coenzyme in a multitude of reactions, including decarboxylation, deamination and transamination [, , ]. PLP-dependent enzymes are primarily involved in the biosynthesis of amino acids and amino acid-derived metabolites, but they are also found in the biosynthetic pathways of amino sugars and in the synthesis or catabolism of neurotransmitters; pyridoxal phosphate can also inhibit DNA polymerases and several steroid receptors []. Inadequate levels of pyridoxal phosphate in the brain can cause neurological dysfunction, particularly epilepsy [].PLP enzymes exist in their resting state as a Schiff base, the aldehyde group of PLP forming a linkage with the ε-amino group of an active site lysine residue on the enzyme. The α-amino group of the substrate displaces the lysine ε-amino group, in the process forming a new aldimine with the substrate. This aldimine is the common central intermediate for all PLP-catalysed reactions, enzymatic and non-enzymatic [].In Escherichia coli, the pdx genes involved in vitamin B6 have been characterised [, , ]. This entry represents PdxJ (also called PNP synthase), which catalyses the condensation of 4-hydroxy-L-threonine and 1-deoxy-D-xylulose-5-phosphate to form pyridoxine-5'-phosphate (PNP) []. The product of the PdxJ reaction is then oxidized by PdxH to form pyridoxal 5'-phosphate (PLP).PNP synthase (PdxJ) adopts a TIM barrel topology. Intersubunit contacts are mediated by three ''extra'' helices, generating a tetramer of symmetric dimers with shared active sites. The open state has been proposed to accept substrates and to release products, while most of the catalytic events are likely to occur in the closed state. A hydrophilic channel running through the centre of the barrel was identified as the essential structural feature that enables PNP synthase to release water molecules produced during the reaction from the closed, solvent-shielded active site [].
Synucleins are small, soluble proteins expressed primarily in neural tissue and in certain tumors [, ]. The family includes three known proteins: alpha-synuclein, beta-synuclein, and gamma-synuclein. All synucleins have in common a highly conserved α-helical lipid-binding motif with similarity to the class-A2 lipid-binding domains of the exchangeable apolipoproteins [].Synuclein family members are not found outside vertebrates, although they have some conserved structural similarity with plant 'late-embryo-abundant' proteins. The alpha- and beta-synuclein proteins are found primarily in brain tissue, where they are seen mainly in presynaptic terminals [, ]. The gamma-synuclein protein is found primarily in the peripheral nervous system and retina, but its expression in breast tumors []is a marker for tumor progression [].Normal cellular functions have not been determined for any of the synuclein proteins,although some data suggest a role in the regulation of membrane stability and/or turnover.Mutations in alpha-synuclein are associated with rare familial cases of early-onset Parkinson'sdisease, and the protein accumulates abnormally in Parkinson's disease, Alzheimer's disease,and several other neurodegenerative illnesses []. Beta-synuclein, also known as PNP 14, is expressed in the brain, specifically in synapses aroundneurons, but not in glial cells. The protein, which has been designateda phosphoneuroprotein, has been found to be phosphorylated in vitro and invivo []. It is believed that the physiological functions of beta-synuclein may be controlled by the phosphorylation reaction.
