This entry represents D-aminopeptidase that hydrolyses N-terminal residues in D-amino acid-containing peptides ().D-aminopeptidase is a dimeric enzyme with each monomer being composed of three domains; domain B is connected to domain A, the catalytic domain, by an eight-residue sequence, and also interacts with both domains A and C via non-covalent bonds. Domain B probably functions in maintaining domain C in a good position to interact with the catalytic domain [].
PrpF is a protein found in the 2-methylcitrate pathway. It is structurally similar to DAP epimerase and proline racemase. This protein is an aconitate- isomerise converting trans-aconitate to cis-aconitate [, ].
Centriole distal appendages (DAPs) anchor cilia to the plasma membrane and are thought to initiate primary cilium assembly through ciliary vesicles docking to the mother centriole. Centrosomal protein of 83kDa (Cep83), previously known as coiled-coil domain-containing protein 41 or CCDC41, is a DAP component required for the docking of ciliary vesicles []. Cep38 has been shown to recruit SCLT1 and Cep89, also DAP components, to centrioles [].
Aminotransferases share certain mechanistic features with other pyridoxal-phosphate dependent enzymes, such as the covalent binding of the pyridoxal-phosphate group to a lysine residue. On the basis of sequence similarity, these various enzymes can be grouped []into class I and class II. This entry includes proteins from both subfamilies, including class I LL-diaminopimelate aminotransferase, chloroplastic from Arabidopsis thaliana (Dap) and class II Histidinol-phosphate aminotransferase from Listeria welshimeri (HisC). Dap consists of two domains, a large domain and a small domain. This entry represents the large domain, which has a 3-layer α/β/α sandwich topology [].
This entry contains the D-aminopeptidase dipeptide-binding protein (dppA; DAP dppA; MEROPS identifier M55.001). Peptide transport systems are found in many bacterial species and generally function to accumulate intact peptides in the cell, where they are hydrolyzed []. The dipeptide-binding protein (dppA) of Bacillus subtilis belongs to the dipeptide ABC transport (dpp) operon expressed early during sporulation. It is a binuclear zinc-dependent, D-specific aminopeptidase. The biologically active enzyme is a homodecamer with active sites buried in its channel. These self-compartmentalizing proteases are characterized by a SXDXEG motif []. D-Ala-D-Ala and D-Ala-Gly-Gly are the preferred substrates []. Bacillus subtilis dppA is thought to function as an adaptation to nutrient deficiency; hydrolysis of its substrate releases D-Ala which can be used subsequently as metabolic fuel [].
Beta-Lactam antibiotics interfere with the biosynthesis of peptidoglycans in the bacterial cell wall by inactivating the penicillin-binding proteins DD-transpeptidases. Bacterial resistance to beta-lactam occurs through the synthesis of beta-lactmases that hydrolyse beta-lactam rings. D-aminopeptidase (DAP; peptidase family S12) is inhibited by beta-lactam antibiotics, and shares a low sequence identity with class C beta-lactamases and R61 DD-carboxypeptidase. DAP consists of three domains: the N-terminal domain A contains catalytic residues and displays a beta-lactamase-like fold (), domains B (middle) and C (C-terminal) domains are structurally similar, displaying an eight-stranded beta barrel []. Domain C is responsible for substrate and inhibitor specificity.This superfamily represents a structurally similar domain to domains B and C of D-aminopeptidase. Proteins in this entry include D-aminopeptidases and some uncharacterised hypothetical lipoproteins from Streptococcus.
Two lysine biosynthesis pathways evolved separately in organisms, the diaminopimelic acid (DAP) and aminoadipic acid (AAA) pathways. The DAP pathway synthesizes L-lysine from aspartate and pyruvate, and diaminopimelic acid is an intermediate. This pathway is utilised by most bacteria, some archaea, some fungi, some algae, and plants. The AAA pathway synthesizes L-lysine from alpha-ketoglutarate and acetyl coenzyme A (acetyl-CoA), and alpha-aminoadipic acid is an intermediate. This pathway is utilised by most fungi, some algae, the bacterium Thermus thermophilus, and probably some archaea, such as Sulfolobus, Thermoproteus, and Pyrococcus. No organism is known to possess both pathways [].There four known variations of the DAP pathway in bacteria: the succinylase, acetylase, aminotransferase, and dehydrogenase pathways. These pathways share the steps converting L-aspartate to L-2,3,4,5- tetrahydrodipicolinate (THDPA), but the subsequent steps leading to the production of meso-diaminopimelate, the immediate precursor of L-lysine, are different [].The succinylase pathway acylates THDPA with succinyl-CoA to generate N-succinyl-LL-2-amino-6-ketopimelate and forms meso-DAP by subsequent transamination, desuccinylation, and epimerization. This pathway is utilised by proteobacteria and many firmicutes and actinobacteria. The acetylase pathway is analogous to the succinylase pathway but uses N-acetyl intermediates. This pathway is limited to certain Bacillus species, in which the corresponding genes have not been identified. The aminotransferase pathway converts THDPA directly to LL-DAP by diaminopimelate aminotransferase (DapL) without acylation. This pathway is shared by cyanobacteria, Chlamydia, the archaeon Methanothermobacter thermautotrophicus, and the plant Arabidopsis thaliana. The dehydrogenase pathway forms meso-DAP directly from THDPA, NADPH, and NH4 _ by using diaminopimelate dehydrogenase (Ddh). This pathway is utilised by some Bacillus and Brevibacterium species and Corynebacterium glutamicum. Most bacteria use only one of the four variants, although certain bacteria, such as C. glutamicum and Bacillus macerans, possess both the succinylase and dehydrogenase pathways.This entry represents the diaminopimelate dehydrogenase enzyme which provides an alternate (shortcut) route of lysine biosynthesis in Corynebacterium, Bacterioides, Porphyromonas and other species. The enzyme from Corynebacterium glutamicum (Brevibacterium flavum) has been crystallized and characterised [].
Two lysine biosynthesis pathways evolved separately in organisms, the diaminopimelic acid (DAP) and aminoadipic acid (AAA) pathways. The DAP pathway synthesizes L-lysine from aspartate and pyruvate, and diaminopimelic acid is an intermediate. This pathway is utilised by most bacteria, some archaea, some fungi, some algae, and plants. The AAA pathway synthesizes L-lysine from alpha-ketoglutarate and acetyl coenzyme A (acetyl-CoA), and alpha-aminoadipic acid is an intermediate. This pathway is utilised by most fungi, some algae, the bacterium Thermus thermophilus, and probably some archaea, such as Sulfolobus, Thermoproteus, and Pyrococcus. No organism is known to possess both pathways [].There four known variations of the DAP pathway in bacteria: the succinylase, acetylase, aminotransferase, and dehydrogenase pathways. These pathways share the steps converting L-aspartate to L-2,3,4,5- tetrahydrodipicolinate (THDPA), but the subsequent steps leading to the production of meso-diaminopimelate, the immediate precursor of L-lysine, are different [].The succinylase pathway acylates THDPA with succinyl-CoA to generate N-succinyl-LL-2-amino-6-ketopimelate and forms meso-DAP by subsequent transamination, desuccinylation, and epimerization. This pathway is utilised by proteobacteria and many firmicutes and actinobacteria. The acetylase pathway is analogous to the succinylase pathway but uses N-acetyl intermediates. This pathway is limited to certain Bacillus species, in which the corresponding genes have not been identified. The aminotransferase pathway converts THDPA directly to LL-DAP by diaminopimelate aminotransferase (DapL) without acylation. This pathway is shared by cyanobacteria, Chlamydia, the archaeon Methanothermobacter thermautotrophicus, and the plant Arabidopsis thaliana. The dehydrogenase pathway forms meso-DAP directly from THDPA, NADPH, and NH4 _ by using diaminopimelate dehydrogenase (Ddh). This pathway is utilised by some Bacillus and Brevibacterium species and Corynebacterium glutamicum. Most bacteria use only one of the four variants, although certain bacteria, such as C. glutamicum and Bacillus macerans, possess both the succinylase and dehydrogenase pathways.This family of succinyldiaminopimelate transaminases (DapC) includes the experimentally characterised enzyme from Bordetella pertussis []. The majority of genes in this family are proximal to genes encoding components of the lysine biosynthesis via succinylase diaminopimelate pathway () [].
Two lysine biosynthesis pathways evolved separately in organisms, the diaminopimelic acid (DAP) and aminoadipic acid (AAA) pathways. The DAP pathway synthesizes L-lysine from aspartate and pyruvate, and diaminopimelic acid is an intermediate. This pathway is utilised by most bacteria, some archaea, some fungi, some algae, and plants. The AAA pathway synthesizes L-lysine from alpha-ketoglutarate and acetyl coenzyme A (acetyl-CoA), and alpha-aminoadipic acid is an intermediate. This pathway is utilised by most fungi, some algae, the bacterium Thermus thermophilus, and probably some archaea, such as Sulfolobus, Thermoproteus, and Pyrococcus. No organism is known to possess both pathways [].There four known variations of the DAP pathway in bacteria: the succinylase, acetylase, aminotransferase, and dehydrogenase pathways. These pathways share the steps converting L-aspartate to L-2,3,4,5- tetrahydrodipicolinate (THDPA), but the subsequent steps leading to the production of meso-diaminopimelate, the immediate precursor of L-lysine, are different [].The succinylase pathway acylates THDPA with succinyl-CoA to generate N-succinyl-LL-2-amino-6-ketopimelate and forms meso-DAP by subsequent transamination, desuccinylation, and epimerization. This pathway is utilised by proteobacteria and many firmicutes and actinobacteria. The acetylase pathway is analogous to the succinylase pathway but uses N-acetyl intermediates. This pathway is limited to certain Bacillus species, in which the corresponding genes have not been identified. The aminotransferase pathway converts THDPA directly to LL-DAP by diaminopimelate aminotransferase (DapL) without acylation. This pathway is shared by cyanobacteria, Chlamydia, the archaeon Methanothermobacter thermautotrophicus, and the plant Arabidopsis thaliana. The dehydrogenase pathway forms meso-DAP directly from THDPA, NADPH, and NH4 _ by using diaminopimelate dehydrogenase (Ddh). This pathway is utilised by some Bacillus and Brevibacterium species and Corynebacterium glutamicum. Most bacteria use only one of the four variants, although certain bacteria, such as C. glutamicum and Bacillus macerans, possess both the succinylase and dehydrogenase pathways.This entry represents acetyldiaminopimelate deacetylase, which converts N-acetyl-L-2-amino-6-diaminopimelate to L,L-DAP. It is the last step of the lysine biosynthesis acetylase pathway.
Two lysine biosynthesis pathways evolved separately in organisms, the diaminopimelic acid (DAP) and aminoadipic acid (AAA) pathways. The DAP pathway synthesizes L-lysine from aspartate and pyruvate, and diaminopimelic acid is an intermediate. This pathway is utilised by most bacteria, some archaea, some fungi, some algae, and plants. The AAA pathway synthesizes L-lysine from alpha-ketoglutarate and acetyl coenzyme A (acetyl-CoA), and alpha-aminoadipic acid is an intermediate. This pathway is utilised by most fungi, some algae, the bacterium Thermus thermophilus, and probably some archaea, such as Sulfolobus, Thermoproteus, and Pyrococcus. No organism is known to possess both pathways [].There four known variations of the DAP pathway in bacteria: the succinylase, acetylase, aminotransferase, and dehydrogenase pathways. These pathways share the steps converting L-aspartate to L-2,3,4,5- tetrahydrodipicolinate (THDPA), but the subsequent steps leading to the production of meso-diaminopimelate, the immediate precursor of L-lysine, are different [].The succinylase pathway acylates THDPA with succinyl-CoA to generate N-succinyl-LL-2-amino-6-ketopimelate and forms meso-DAP by subsequent transamination, desuccinylation, and epimerization. This pathway is utilised by proteobacteria and many firmicutes and actinobacteria. The acetylase pathway is analogous to the succinylase pathway but uses N-acetyl intermediates. This pathway is limited to certain Bacillus species, in which the corresponding genes have not been identified. The aminotransferase pathway converts THDPA directly to LL-DAP by diaminopimelate aminotransferase (DapL) without acylation. This pathway is shared by cyanobacteria, Chlamydia, the archaeon Methanothermobacter thermautotrophicus, and the plant Arabidopsis thaliana. The dehydrogenase pathway forms meso-DAP directly from THDPA, NADPH, and NH4 _ by using diaminopimelate dehydrogenase (Ddh). This pathway is utilised by some Bacillus and Brevibacterium species and Corynebacterium glutamicum. Most bacteria use only one of the four variants, although certain bacteria, such as C. glutamicum and Bacillus macerans, possess both the succinylase and dehydrogenase pathways.This entry represents a clade of succinyl-diaminopimelate desuccinylases from actinobacteria (high-GC Gram-positives) and is based on the characterisation of the enzyme from Corynebacterium glutamicum (Brevibacterium flavum) []. This enzyme is involved in the biosynthesis of lysine, and is related to the enzyme acetylornithine deacetylase and other amidases and peptidases. They are classified as non-peptidases homologues belonging to MEROPS peptidase family M20A
Two lysine biosynthesis pathways evolved separately in organisms, the diaminopimelic acid (DAP) and aminoadipic acid (AAA) pathways. The DAP pathway synthesizes L-lysine from aspartate and pyruvate, and diaminopimelic acid is an intermediate. This pathway is utilised by most bacteria, some archaea, some fungi, some algae, and plants. The AAA pathway synthesizes L-lysine from alpha-ketoglutarate and acetyl coenzyme A (acetyl-CoA), and alpha-aminoadipic acid is an intermediate. This pathway is utilised by most fungi, some algae, the bacterium Thermus thermophilus, and probably some archaea, such as Sulfolobus, Thermoproteus, and Pyrococcus. No organism is known to possess both pathways [].There four known variations of the DAP pathway in bacteria: the succinylase, acetylase, aminotransferase, and dehydrogenase pathways. These pathways share the steps converting L-aspartate to L-2,3,4,5- tetrahydrodipicolinate (THDPA), but the subsequent steps leading to the production of meso-diaminopimelate, the immediate precursor of L-lysine, are different [].The succinylase pathway acylates THDPA with succinyl-CoA to generate N-succinyl-LL-2-amino-6-ketopimelate and forms meso-DAP by subsequent transamination, desuccinylation, and epimerization. This pathway is utilised by proteobacteria and many firmicutes and actinobacteria. The acetylase pathway is analogous to the succinylase pathway but uses N-acetyl intermediates. This pathway is limited to certain Bacillus species, in which the corresponding genes have not been identified. The aminotransferase pathway converts THDPA directly to LL-DAP by diaminopimelate aminotransferase (DapL) without acylation. This pathway is shared by cyanobacteria, Chlamydia, the archaeon Methanothermobacter thermautotrophicus, and the plant Arabidopsis thaliana. The dehydrogenase pathway forms meso-DAP directly from THDPA, NADPH, and NH4 _ by using diaminopimelate dehydrogenase (Ddh). This pathway is utilised by some Bacillus and Brevibacterium species and Corynebacterium glutamicum. Most bacteria use only one of the four variants, although certain bacteria, such as C. glutamicum and Bacillus macerans, possess both the succinylase and dehydrogenase pathways.The four sequences which make up the seed for this model are not closely related, although they are all members of the family of aminotransferases and are more closely related to each other than to anything else. Additionally, all of them are found in the vicinity of genes involved in the biosynthesis of lysine via the diaminopimelate pathway (), although this amounts to a separation of 12 genes in the case of Sulfurihydrogenibium azorense Az-Fu1. None of these genomes contain another strong candidate for this role in the pathway. Note: the detailed information included in the record includes the assertions that the enzyme uses the pyridoxal pyrophosphate cofactor, which is consistent with the family, and the assertion that the amino group donor is L-glutamate, which is undetermined for the sequences in this clade.
Two lysine biosynthesis pathways evolved separately in organisms, the diaminopimelic acid (DAP) and aminoadipic acid (AAA) pathways. The DAP pathway synthesizes L-lysine from aspartate and pyruvate, and diaminopimelic acid is an intermediate. This pathway is utilised by most bacteria, some archaea, some fungi, some algae, and plants. The AAA pathway synthesizes L-lysine from alpha-ketoglutarate and acetyl coenzyme A (acetyl-CoA), and alpha-aminoadipic acid is an intermediate. This pathway is utilised by most fungi, some algae, the bacterium Thermus thermophilus, and probably some archaea, such as Sulfolobus, Thermoproteus, and Pyrococcus. No organism is known to possess both pathways [].There four known variations of the DAP pathway in bacteria: the succinylase, acetylase, aminotransferase, and dehydrogenase pathways. These pathways share the steps converting L-aspartate to L-2,3,4,5- tetrahydrodipicolinate (THDPA), but the subsequent steps leading to the production of meso-diaminopimelate, the immediate precursor of L-lysine, are different [].The succinylase pathway acylates THDPA with succinyl-CoA to generate N-succinyl-LL-2-amino-6-ketopimelate and forms meso-DAP by subsequent transamination, desuccinylation, and epimerization. This pathway is utilised by proteobacteria and many firmicutes and actinobacteria. The acetylase pathway is analogous to the succinylase pathway but uses N-acetyl intermediates. This pathway is limited to certain Bacillus species, in which the corresponding genes have not been identified. The aminotransferase pathway converts THDPA directly to LL-DAP by diaminopimelate aminotransferase (DapL) without acylation. This pathway is shared by cyanobacteria, Chlamydia, the archaeon Methanothermobacter thermautotrophicus, and the plant Arabidopsis thaliana. The dehydrogenase pathway forms meso-DAP directly from THDPA, NADPH, and NH4 _ by using diaminopimelate dehydrogenase (Ddh). This pathway is utilised by some Bacillus and Brevibacterium species and Corynebacterium glutamicum. Most bacteria use only one of the four variants, although certain bacteria, such as C. glutamicum and Bacillus macerans, possess both the succinylase and dehydrogenase pathways.This group of the superfamily of aminotransferases includes several which are adjacent to elements of the lysine biosynthesis via diaminopimelate pathway (). Every member of this group is from a genome which possesses most of the lysine biosynthesis pathway but lacks any of the known aminotransferases, succinylases, desuccinylases, acetylases or deacetylases typical of the acylated versions of this pathway nor do they have the direct, NADPH-dependent enzyme (ddh). Although there is no experimental characterisation of any of the sequences in this group, a direct pathway is known in plants and Chlamydia [, ]so it seems quite reasonable that these enzymes catalyse the same transformation.
Two lysine biosynthesis pathways evolved separately in organisms, the diaminopimelic acid (DAP) and aminoadipic acid (AAA) pathways. The DAP pathway synthesizes L-lysine from aspartate and pyruvate, and diaminopimelic acid is an intermediate. This pathway is utilised by most bacteria, some archaea, some fungi, some algae, and plants. The AAA pathway synthesizes L-lysine from alpha-ketoglutarate and acetyl coenzyme A (acetyl-CoA), and alpha-aminoadipic acid is an intermediate. This pathway is utilised by most fungi, some algae, the bacterium Thermus thermophilus, and probably some archaea, such as Sulfolobus, Thermoproteus, and Pyrococcus. No organism is known to possess both pathways [].There four known variations of the DAP pathway in bacteria: the succinylase, acetylase, aminotransferase, and dehydrogenase pathways. These pathways share the steps converting L-aspartate to L-2,3,4,5- tetrahydrodipicolinate (THDPA), but the subsequent steps leading to the production of meso-diaminopimelate, the immediate precursor of L-lysine, are different [].The succinylase pathway acylates THDPA with succinyl-CoA to generate N-succinyl-LL-2-amino-6-ketopimelate and forms meso-DAP by subsequent transamination, desuccinylation, and epimerization. This pathway is utilised by proteobacteria and many firmicutes and actinobacteria. The acetylase pathway is analogous to the succinylase pathway but uses N-acetyl intermediates. This pathway is limited to certain Bacillus species, in which the corresponding genes have not been identified. The aminotransferase pathway converts THDPA directly to LL-DAP by diaminopimelate aminotransferase (DapL) without acylation. This pathway is shared by cyanobacteria, Chlamydia, the archaeon Methanothermobacter thermautotrophicus, and the plant Arabidopsis thaliana. The dehydrogenase pathway forms meso-DAP directly from THDPA, NADPH, and NH4 _ by using diaminopimelate dehydrogenase (Ddh). This pathway is utilised by some Bacillus and Brevibacterium species and Corynebacterium glutamicum. Most bacteria use only one of the four variants, although certain bacteria, such as C. glutamicum and Bacillus macerans, possess both the succinylase and dehydrogenase pathways.This entry includes LL-diaminopimelate aminotransferase DapL from bacteria and aminotransferase ALD1 from plants. DapL is involved in the synthesis of meso-diaminopimelate (m-DAP or DL-DAP), required for both lysine and peptidoglycan biosynthesis. This enzyme catalyzes the direct conversion of tetrahydrodipicolinate to LL-diaminopimelate, a reaction that requires three enzymes in E.coli. It is also able to use meso-diaminopimelate, cystathionine, lysine or ornithine as substrates []. ALD1 is involved in the biosynthesis of pipecolate (Pip), a metabolite that orchestrates defense amplification, positive regulation of SA biosynthesis, and priming to guarantee effective local resistance induction and the establishment of SAR [, ].
Two lysine biosynthesis pathways evolved separately in organisms, the diaminopimelic acid (DAP) and aminoadipic acid (AAA) pathways. The DAP pathway synthesizes L-lysine from aspartate and pyruvate, and diaminopimelic acid is an intermediate. This pathway is utilised by most bacteria, some archaea, some fungi, some algae, and plants. The AAA pathway synthesizes L-lysine from alpha-ketoglutarate and acetyl coenzyme A (acetyl-CoA), and alpha-aminoadipic acid is an intermediate. This pathway is utilised by most fungi, some algae, the bacterium Thermus thermophilus, and probably some archaea, such as Sulfolobus, Thermoproteus, and Pyrococcus. No organism is known to possess both pathways [].There four known variations of the DAP pathway in bacteria: the succinylase, acetylase, aminotransferase, and dehydrogenase pathways. These pathways share the steps converting L-aspartate to L-2,3,4,5- tetrahydrodipicolinate (THDPA), but the subsequent steps leading to the production of meso-diaminopimelate, the immediate precursor of L-lysine, are different [].The succinylase pathway acylates THDPA with succinyl-CoA to generate N-succinyl-LL-2-amino-6-ketopimelate and forms meso-DAP by subsequent transamination, desuccinylation, and epimerization. This pathway is utilised by proteobacteria and many firmicutes and actinobacteria. The acetylase pathway is analogous to the succinylase pathway but uses N-acetyl intermediates. This pathway is limited to certain Bacillus species, in which the corresponding genes have not been identified. The aminotransferase pathway converts THDPA directly to LL-DAP by diaminopimelate aminotransferase (DapL) without acylation. This pathway is shared by cyanobacteria, Chlamydia, the archaeon Methanothermobacter thermautotrophicus, and the plant Arabidopsis thaliana. The dehydrogenase pathway forms meso-DAP directly from THDPA, NADPH, and NH4 _ by using diaminopimelate dehydrogenase (Ddh). This pathway is utilised by some Bacillus and Brevibacterium species and Corynebacterium glutamicum. Most bacteria use only one of the four variants, although certain bacteria, such as C. glutamicum and Bacillus macerans, possess both the succinylase and dehydrogenase pathways.This family of actinobacterial proteins are involved in the biosynthesis of the tetracycline antibiotic, oxytetracycline. The minimum set of enzymes required for the biosynthesis of anhydrotetracycline, the first intermediate in the synthesis of oxytetracycline, are OxyL, OxyQ, and OxyT. OxyQ catalyzes the conversion of 4-dedimethylamino-4-oxoanhydrotetracycline to yield 4-amino-4-de(dimethylamino)anhydrotetracycline (4-amino-ATC) [].
This entry represents the N-terminal catalytic aspartokinase (AK) domain of the lysine-sensitive aspartokinase isoenzyme AKII of Bacillus subtilis 168, the lysine plus threonine-sensitive aspartokinase of Corynebacterium glutamicum, and related sequences. In B. subtilis 168, the regulation of the diaminopimelate (Dap)-lysine biosynthetic pathway involves dual control by Dap and lysine, effected through separate Dap- and lysine-sensitive aspartokinase isoenzymes. The B. subtilis 168 AKII is induced by methionine, and repressed and inhibited by lysine. Although Corynebacterium glutamicum is known to contain a single aspartokinase isoenzyme type, both the succinylase and dehydrogenase variant pathways of DAP-lysine synthesis operate simultaneously in this organism. In this organism and other various Gram-positive bacteria, the DAP-lysine pathway is feedback regulated by the concerted action of lysine and threonine. Also included in this entry are the aspartokinases of the extreme thermophile, Thermus thermophilus HB27, the Gram-negative obligate methylotroph, Methylophilus methylotrophus AS1, and those single aspartokinases found in Pseudomons, C. glutamicum, and Amycolatopsis lactamdurans. B. subtilis 168 AKII, and the C. glutamicum, Streptomyces clavuligerus and A. lactamdurans aspartokinases are described as tetramers consisting of two alpha and two beta subunits; the alpha (44 kD) and beta (18 kD) subunits formed by two in-phase overlapping polypeptides [, , , , , , , , , , ].
Pyridoxal-dependent decarboxylases that act on ornithine-, lysine-, arginine- and related substrates can be classified into different familieson the basis of sequence similarity [, ]. One of these families includesornithine decarboxylase (ODC), which catalyses the transformationof ornithine into putrescine; prokaryotic diaminopimelate decarboxylase, which catalyses the conversion of diaminopimelate into lysine; Pseudomonas syringae pv. tabaciprotein, tabA, which is probably involved in tabtoxin biosynthesis andis similar to diaminopimelate decarboxylase; and bacterial and plant biosynthetic argininedecarboxylase, which catalyses the transformation of arginine into agmatine, the first step in putrescine synthesis from arginine.Although these proteins, which are known collectively as group IVdecarboxylases [], probably share a common evolutionary origin, theirlevels of sequence similarity are low, being confined to a few shortconserved regions. These conserved motifs suggest a common structuralarrangement for positioning of substrate and the cofactor pyridoxal5'-phosphate among bacterial diaminopimelate ddecarboxylases, eukaryotic ornithinedecarboxylases and arginine decarboxylases [].This entry represents the diaminopimelate decarboxylase LysA, which converts meso-diaminopimelate into lysine and is the last step of the DAP lysine biosynthetic pathway. The structure of bacterial diaminopimelate decarboxylase has been determined [].
Bacteria, plants and fungi metabolise aspartic acid to produce four amino acids - lysine, threonine, methionine and isoleucine - in a series of reactions known as the aspartate pathway. Additionally, several important metabolic intermediates are produced by these reactions, such as diaminopimelic acid, an essential component of bacterial cell wall biosynthesis, and dipicolinic acid, which is involved in sporulation in Gram-positive bacteria. Members of the animal kingdom do not posses this pathway and must therefore acquire these essential amino acids through their diet. Research into improving the metabolic flux through this pathway has the potential to increase the yield of the essential amino acids in important crops, thus improving their nutritional value. Additionally, since the enzymes are not present in animals, inhibitors of them are promising targets for the development of novel antibiotics and herbicides. For more information see [].Two lysine biosynthesis pathways evolved separately in organisms, the diaminopimelic acid (DAP) and aminoadipic acid (AAA) pathways. The DAP pathway synthesizes L-lysine from aspartate and pyruvate, and diaminopimelic acid is an intermediate. This pathway is utilised by most bacteria, some archaea, some fungi, some algae, and plants. The AAA pathway synthesizes L-lysine from alpha-ketoglutarate and acetyl coenzyme A (acetyl-CoA), and alpha-aminoadipic acid is an intermediate. This pathway is utilised by most fungi, some algae, the bacterium Thermus thermophilus, and probably some archaea, such as Sulfolobus, Thermoproteus, and Pyrococcus. No organism is known to possess both pathways [].There four known variations of the DAP pathway in bacteria: the succinylase, acetylase, aminotransferase, and dehydrogenase pathways. These pathways share the steps converting L-aspartate to L-2,3,4,5- tetrahydrodipicolinate (THDPA), but the subsequent steps leading to the production of meso-diaminopimelate, the immediate precursor of L-lysine, are different [].The succinylase pathway acylates THDPA with succinyl-CoA to generate N-succinyl-LL-2-amino-6-ketopimelate and forms meso-DAP by subsequent transamination, desuccinylation, and epimerization. This pathway is utilised by proteobacteria and many firmicutes and actinobacteria. The acetylase pathway is analogous to the succinylase pathway but uses N-acetyl intermediates. This pathway is limited to certain Bacillus species, in which the corresponding genes have not been identified. The aminotransferase pathway converts THDPA directly to LL-DAP by diaminopimelate aminotransferase (DapL) without acylation. This pathway is shared by cyanobacteria, Chlamydia, the archaeon Methanothermobacter thermautotrophicus, and the plant Arabidopsis thaliana. The dehydrogenase pathway forms meso-DAP directly from THDPA, NADPH, and NH4 _ by using diaminopimelate dehydrogenase (Ddh). This pathway is utilised by some Bacillus and Brevibacterium species and Corynebacterium glutamicum. Most bacteria use only one of the four variants, although certain bacteria, such as C. glutamicum and Bacillus macerans, possess both the succinylase and dehydrogenase pathways.2,3,4,5-tetrahydropyridine-2,6-dicarboxylate N-succinyltransferase (also known as tetrahydrodipicolinate N-succinyltransferase or DapD) is part of the succinyl route of of lysine/DAP biosynthesis. The DapD protein is a homotrimer is a trimeric enzyme with each monomer composed of three domain: an N-terminal helical domain, a distinctive left-handed parallel β-helix (LBH) domain, and a predominantly beta C-terminal domain [, ]. The LBH structure is encoded by an imperfect tandem-repeated hexapeptide sequence. Each trimer contains three independent active sites, always occuring at the boundary of two subunits, and formed by residues from one N-terminal domain, one C-terminal domain and two adjacent LBH domains.
Bacteria, plants and fungi metabolise aspartic acid to produce four amino acids - lysine, threonine, methionine and isoleucine - in a series of reactions known as the aspartate pathway. Additionally, several important metabolic intermediates are produced by these reactions, such as diaminopimelic acid, an essential component of bacterial cell wall biosynthesis, and dipicolinic acid, which is involved in sporulation in Gram-positive bacteria. Members of the animal kingdom do not posses this pathway and must therefore acquire these essential amino acids through their diet. Research into improving the metabolic flux through this pathway has the potential to increase the yield of the essential amino acids in important crops, thus improving their nutritional value. Additionally, since the enzymes are not present in animals, inhibitors of them are promising targets for the development of novel antibiotics and herbicides. For more information see [].Two lysine biosynthesis pathways evolved separately in organisms, the diaminopimelic acid (DAP) and aminoadipic acid (AAA) pathways. The DAP pathway synthesizes L-lysine from aspartate and pyruvate, and diaminopimelic acid is an intermediate. This pathway is utilised by most bacteria, some archaea, some fungi, some algae, and plants. The AAA pathway synthesizes L-lysine from alpha-ketoglutarate and acetyl coenzyme A (acetyl-CoA), and alpha-aminoadipic acid is an intermediate. This pathway is utilised by most fungi, some algae, the bacterium Thermus thermophilus, and probably some archaea, such as Sulfolobus, Thermoproteus, and Pyrococcus. No organism is known to possess both pathways [].There four known variations of the DAP pathway in bacteria: the succinylase, acetylase, aminotransferase, and dehydrogenase pathways. These pathways share the steps converting L-aspartate to L-2,3,4,5- tetrahydrodipicolinate (THDPA), but the subsequent steps leading to the production of meso-diaminopimelate, the immediate precursor of L-lysine, are different [].The succinylase pathway acylates THDPA with succinyl-CoA to generate N-succinyl-LL-2-amino-6-ketopimelate and forms meso-DAP by subsequent transamination, desuccinylation, and epimerization. This pathway is utilised by proteobacteria and many firmicutes and actinobacteria. The acetylase pathway is analogous to the succinylase pathway but uses N-acetyl intermediates. This pathway is limited to certain Bacillus species, in which the corresponding genes have not been identified. The aminotransferase pathway converts THDPA directly to LL-DAP by diaminopimelate aminotransferase (DapL) without acylation. This pathway is shared by cyanobacteria, Chlamydia, the archaeon Methanothermobacter thermautotrophicus, and the plant Arabidopsis thaliana. The dehydrogenase pathway forms meso-DAP directly from THDPA, NADPH, and NH4 _ by using diaminopimelate dehydrogenase (Ddh). This pathway is utilised by some Bacillus and Brevibacterium species and Corynebacterium glutamicum. Most bacteria use only one of the four variants, although certain bacteria, such as C. glutamicum and Bacillus macerans, possess both the succinylase and dehydrogenase pathways.This entry represents diaminopimelate epimerase (), which catalyses the isomerisation of L,L-dimaminopimelate to meso-DAP in the biosynthetic pathway leading from aspartate to lysine. It is a member of the broader family of PLP-independent amino acid racemases. This enzyme is a monomeric protein of about 30kDa consisting of two domains which are homologus in structure though they share little sequence similarity []. Each domain consists of mixed β-sheets which fold into a barrel around the central helix. The active site cleft is formed from both domains and contains two conserved cysteines thought to function as the acid and base in the catalytic reaction []. Other PLP-independent racemases such as glutamate racemase have been shown to share a similar structure and mechanism of catalysis.
