Type III Pyridoxal 5-phosphate (PLP)-Dependent Enzymes; The fold type III PLP-dependent enzyme family is predominantly composed of two-domain proteins with similarity to bacterial alanine racemases (AR) including eukaryotic ornithine decarboxylases (ODC), prokaryotic diaminopimelate decarboxylases (DapDC), biosynthetic arginine decarboxylases (ADC), carboxynorspermidine decarboxylases (CANSDC), and similar proteins. AR-like proteins contain an N-terminal PLP-binding TIM-barrel domain and a C-terminal beta-sandwich domain. They exist as homodimers with active sites that lie at the interface between the TIM barrel domain of one subunit and the beta-sandwich domain of the other subunit. These proteins play important roles in the biosynthesis of amino acids and polyamine. The family also includes the single-domain YBL036c-like proteins, which contain a single PLP-binding TIM-barrel domain without any N- or C-terminal extensions. Due to the lack of a second domain, these proteins may possess only limited D- to L-alanine racemase activity or non-specific racemase activity.

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gi 306959828   1 LKTSRLLLERAKELDLAIVGVSFHVGSGCTDPETFVQAI*DARCVFDMGAELGFSMYLLDIG 62
Cdd:cd00622  138 PEEARELLRRAKELGLNVVGVSFHVGSQCTDPSAYVDAIADAREVFDEAAELGFKLKLLDIG 199

Type III Pyridoxal 5-phosphate (PLP)-Dependent Enzyme Ornithine Decarboxylase; This subfamily is composed mainly of eukaryotic ornithine decarboxylases (ODC, EC 4.1.1.17) and ODC-like enzymes from prokaryotes represented by Vibrio vulnificus LysineOrnithine decarboxylase. These are fold type III PLP-dependent enzymes that differ from most bacterial ODCs which are fold type I PLP-dependent enzymes. ODC participates in the formation of putrescine by catalyzing the decarboxylation of ornithine, the first step in polyamine biosynthesis. Members of this subfamily contain an N-terminal PLP-binding TIM-barrel domain and a C-terminal beta-sandwich domain, similar to bacterial alanine racemases. They exist as homodimers with active sites that lie at the interface between the TIM barrel domain of one subunit and the beta-sandwich domain of the other subunit. Homodimer formation and the presence of the PLP cofactor are required for catalytic activity. Also members of this subfamily are proteins with homology to ODC but do not possess any catalytic activity, the Antizyme inhibitor (AZI) and ODC-paralogue (ODC-p). AZI binds to the regulatory protein Antizyme with a higher affinity than ODC and prevents ODC degradation. ODC-p is a novel ODC-like protein, present only in mammals, that is specifically exressed in the brain and testes. ODC-p may function as a tissue-specific antizyme inhibitory protein.

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                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 306959828   1 LKTSRLLLERAKELDLAIVGVSFHVGSGCTDPETFVQAI*DARCVFDMGAELGFSMYLLDIG 62
Cdd:cd00622  138 PEEARELLRRAKELGLNVVGVSFHVGSQCTDPSAYVDAIADAREVFDEAAELGFKLKLLDIG 199

bifunctional aspartate kinase/diaminopimelate decarboxylase;

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gi 306959828   7 LLERAKELDLAIVGVSFHVGSGCTDPETFVQ 37
Cdd:PRK08961 652 FVDLAKTLGITVVGLHAHLGSGIETGEHWRR 682

Type III Pyridoxal 5-phosphate (PLP)-Dependent Enzyme Ornithine Decarboxylase; This subfamily is composed mainly of eukaryotic ornithine decarboxylases (ODC, EC 4.1.1.17) and ODC-like enzymes from prokaryotes represented by Vibrio vulnificus LysineOrnithine decarboxylase. These are fold type III PLP-dependent enzymes that differ from most bacterial ODCs which are fold type I PLP-dependent enzymes. ODC participates in the formation of putrescine by catalyzing the decarboxylation of ornithine, the first step in polyamine biosynthesis. Members of this subfamily contain an N-terminal PLP-binding TIM-barrel domain and a C-terminal beta-sandwich domain, similar to bacterial alanine racemases. They exist as homodimers with active sites that lie at the interface between the TIM barrel domain of one subunit and the beta-sandwich domain of the other subunit. Homodimer formation and the presence of the PLP cofactor are required for catalytic activity. Also members of this subfamily are proteins with homology to ODC but do not possess any catalytic activity, the Antizyme inhibitor (AZI) and ODC-paralogue (ODC-p). AZI binds to the regulatory protein Antizyme with a higher affinity than ODC and prevents ODC degradation. ODC-p is a novel ODC-like protein, present only in mammals, that is specifically exressed in the brain and testes. ODC-p may function as a tissue-specific antizyme inhibitory protein.

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gi 306959828   1 LKTSRLLLERAKELDLAIVGVSFHVGSGCTDPETFVQAI*DARCVFDMGAELGFSMYLLDIG 62
Cdd:cd00622  138 PEEARELLRRAKELGLNVVGVSFHVGSQCTDPSAYVDAIADAREVFDEAAELGFKLKLLDIG 199

Type III Pyridoxal 5-phosphate (PLP)-Dependent Enzyme Ornithine Decarboxylase-like Antizyme Inhibitor; Antizyme inhibitor (AZI) is homologous to the fold type III PLP-dependent enzyme ODC but does not retain any decarboxylase activity. Like ODC, AZI is presumed to exist as a homodimer. Antizyme is a regulatory protein that binds directly to the ODC monomer to block its active site, leading to its degradation by the 26S proteasome. AZI binds to Antizyme with a higher affinity than ODC, preventing the formation of the Antizyme-ODC complex. Thus, AZI blocks the ability of Antizyme to promote ODC degradation, which leads to increased ODC enzymatic activity and polyamine levels. AZI also prevents the degradation of other proteins regulated by Antizyme, such as cyclin D1.

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gi 306959828   1 LKTSRLLLERAKELDLAIVGVSFHVGSGCTDPETFVQAI*DARCVFDMGAELGFSMYLLDIG 62
Cdd:cd06831  149 LKNCRHLLECAKELDVQIVGVKFHVSSSCKEYQTYVHALSDARCVFDMAEEFGFKMNMLDIG 210

Type III Pyridoxal 5-phosphate (PLP)-Dependent Enzymes, Ornithine and Diaminopimelate Decarboxylases, and Related Enzymes; This family includes eukaryotic ornithine decarboxylase (ODC, EC 4.1.1.17), diaminopimelate decarboxylase (DapDC, EC 4.1.1.20), plant and prokaryotic biosynthetic arginine decarboxylase (ADC, EC 4.1.1.19), carboxynorspermidine decarboxylase (CANSDC), and ODC-like enzymes from diverse bacterial species. These proteins are fold type III PLP-dependent enzymes that catalyze essential steps in the biosynthesis of polyamine and lysine. ODC and ADC participate in alternative pathways of the biosynthesis of putrescine, which is the precursor of aliphatic polyamines in many organisms. ODC catalyzes the direct synthesis of putrescine from L-ornithine, while ADC converts L-arginine to agmatine, which is hydrolysed to putrescine by agmatinase in a pathway that exists only in plants and bacteria. DapDC converts meso-2,6-diaminoheptanedioate to L-lysine, which is the final step of lysine biosynthesis. CANSDC catalyzes the decarboxylation of carboxynorspermidine, which is the last step in the synthesis of norspermidine. The PLP-dependent decarboxylases in this family contain an N-terminal PLP-binding TIM-barrel domain and a C-terminal beta-sandwich domain, similar to bacterial alanine racemases. They exist as homodimers with active sites that lie at the interface between the TIM barrel domain of one subunit and the beta-sandwich domain of the other subunit. Prokaryotic ornithine, lysine and biodegradative arginine decarboxylases are fold type I PLP-dependent enzymes and are not included in this family.

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gi 306959828   1 LKTSRLLLERAKELDLAIVGVSFHVGSGCTDPETFVQAI*DARCVFDMGAELGFSMYLLDIG 62
Cdd:cd06810  147 LSEARAALERAKELDLRLVGLHFHVGSQILDLETIVQALSDARELIEELVEMGFPLEMLDLG 208

Type III Pyridoxal 5-phosphate (PLP)-Dependent Enzyme Diaminopimelate Decarboxylase; Diaminopimelate decarboxylase (DapDC, EC 4.1.1.20) participates in the last step of lysine biosynthesis. It converts meso-2,6-diaminoheptanedioate to L-lysine. It is a fold type III PLP-dependent enzyme that contains an N-terminal PLP-binding TIM-barrel domain and a C-terminal beta-sandwich domain, similar to bacterial alanine racemases. DapDC exists as homodimers with active sites that lie at the interface between the TIM barrel domain of one subunit and the beta-sandwich domain of the other subunit. Homodimer formation and the presence of the PLP cofactor are required for catalytic activity.

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gi 306959828   7 LLERAKELD-LAIVGVSFHVGSGCTDPETFVQAi*dARCVFDMGAEL---GFSMYLLDIG 62
Cdd:cd06828  157 AYRRAKELPgLKLVGLHCHIGSQILDLEPFVEA---AEKLLDLAAELrelGIDLEFLDLG 213

bifunctional aspartate kinase/diaminopimelate decarboxylase;

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gi 306959828   7 LLERAKELDLAIVGVSFHVGSGCTDPETFVQ 37
Cdd:PRK08961 652 FVDLAKTLGITVVGLHAHLGSGIETGEHWRR 682