diaminopimelate epimerase | |||||||||
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Identifiers | |||||||||
EC no. | 5.1.1.7 | ||||||||
CAS no. | 9024-22-0 | ||||||||
Databases | |||||||||
IntEnz | IntEnz view | ||||||||
BRENDA | BRENDA entry | ||||||||
ExPASy | NiceZyme view | ||||||||
KEGG | KEGG entry | ||||||||
MetaCyc | metabolic pathway | ||||||||
PRIAM | profile | ||||||||
PDB structures | RCSB PDB PDBe PDBsum | ||||||||
Gene Ontology | AmiGO / QuickGO | ||||||||
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Diaminopimelate epimerase | |||||||||||
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Identifiers | |||||||||||
Symbol | DAP_epimerase | ||||||||||
Pfam | PF01678 | ||||||||||
InterPro | IPR001653 | ||||||||||
PROSITE | PDOC01029 | ||||||||||
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In enzymology, a diaminopimelate epimerase (EC 5.1.1.7) is an enzyme that catalyzes the chemical reaction
Hence, this enzyme has one substrate, LL-2,6-diaminoheptanedioate, and one product, meso-diaminoheptanedioate.
This enzyme belongs to the family of isomerases, specifically those racemases and epimerases acting on amino acids and derivatives. The systematic name of this enzyme class is LL-2,6-diaminoheptanedioate 2-epimerase. This enzyme participates in lysine biosynthesis.
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 (spore production) in Gram-positive bacteria. Members of the animal kingdom do not possess 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. [1]
The lysine/diaminopimelic acid branch of the aspartate pathway produces the essential amino acid lysine via the intermediate meso-diaminopimelic acid (meso-DAP), which is also a vital cell wall component in Gram-negative bacteria. [2] The production of dihydropicolinate from aspartate-semialdehyde controls flux into the lysine/diaminopimelic acid pathway. Three variants of this pathway exist, differing in how tetrahydropicolinate (formed by reduction of dihydropicolinate) is metabolised to meso-DAP. One variant, the most commonly found one in archaea and bacteria, uses primarily succinyl intermediates, while a second variant, found only in Bacillus, utilizes primarily acetyl intermediates. In the third variant, found in some Gram-positive bacteria, a dehydrogenase converts tetrahydropicolinate directly to meso-DAP. In all variants meso-DAP is subsequently converted to lysine by a decarboxylase, or, in Gram-negative bacteria, assimilated into the cell wall. Evidence exists that a fourth, currently unknown, variant of this pathway may function in plants. [3]
Diaminopimelate epimerase (EC 5.1.1.7), which catalyses the isomerisation of L,L-dimaminopimelate to meso-DAP in the biosynthetic pathway leading from aspartate to lysine, is a member of the broader family of PLP-independent amino acid racemases. This enzyme is a monomeric protein of about 30 kDa consisting of two domains which are similar in structure though they share little Sequence alignment. [4] Each domain consists of mixed beta-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 Catalysis. [5] Other PLP-independent racemases such as glutamate racemase have been shown to share a similar structure and mechanism of catalysis.
As of late 2007, 4 structures have been solved for this class of enzymes, with PDB accession codes 1BWZ, 1GQZ, 2GKE, and 2GKJ.
Peptidoglycan or murein is a unique large macromolecule, a polysaccharide, consisting of sugars and amino acids that forms a mesh-like peptidoglycan layer outside the plasma membrane, the rigid cell wall characteristic of most bacteria. The sugar component consists of alternating residues of β-(1,4) linked N-acetylglucosamine (NAG) and N-acetylmuramic acid (NAM). Attached to the N-acetylmuramic acid is an oligopeptide chain made of three to five amino acids. The peptide chain can be cross-linked to the peptide chain of another strand forming the 3D mesh-like layer. Peptidoglycan serves a structural role in the bacterial cell wall, giving structural strength, as well as counteracting the osmotic pressure of the cytoplasm. This repetitive linking results in a dense peptidoglycan layer which is critical for maintaining cell form and withstanding high osmotic pressures, and it is regularly replaced by peptidoglycan production. Peptidoglycan hydrolysis and synthesis are two processes that must occur in order for cells to grow and multiply, a technique carried out in three stages: clipping of current material, insertion of new material, and re-crosslinking of existing material to new material.
Lysine (symbol Lys or K) is an α-amino acid that is a precursor to many proteins. It contains an α-amino group (which is in the protonated −NH+
3 form under biological conditions), an α-carboxylic acid group (which is in the deprotonated −COO− form under biological conditions), and a side chain lysyl ((CH2)4NH2), classifying it as a basic, charged (at physiological pH), aliphatic amino acid. It is encoded by the codons AAA and AAG. Like almost all other amino acids, the α-carbon is chiral and lysine may refer to either enantiomer or a racemic mixture of both. For the purpose of this article, lysine will refer to the biologically active enantiomer L-lysine, where the α-carbon is in the S configuration.
Pyridoxal phosphate (PLP, pyridoxal 5'-phosphate, P5P), the active form of vitamin B6, is a coenzyme in a variety of enzymatic reactions. The International Union of Biochemistry and Molecular Biology has catalogued more than 140 PLP-dependent activities, corresponding to ~4% of all classified activities. The versatility of PLP arises from its ability to covalently bind the substrate, and then to act as an electrophilic catalyst, thereby stabilizing different types of carbanionic reaction intermediates.
In molecular biology, biosynthesis is a multi-step, enzyme-catalyzed process where substrates are converted into more complex products in living organisms. In biosynthesis, simple compounds are modified, converted into other compounds, or joined to form macromolecules. This process often consists of metabolic pathways. Some of these biosynthetic pathways are located within a single cellular organelle, while others involve enzymes that are located within multiple cellular organelles. Examples of these biosynthetic pathways include the production of lipid membrane components and nucleotides. Biosynthesis is usually synonymous with anabolism.
Aspartate kinase or aspartokinase (AK) is an enzyme that catalyzes the phosphorylation of the amino acid aspartate. This reaction is the first step in the biosynthesis of three other amino acids: methionine, lysine, and threonine, known as the "aspartate family". Aspartokinases are present only in microorganisms and plants, but not in animals, which must obtain aspartate-family amino acids from their diet. Consequently, methionine, lysine and threonine are essential amino acids in animals.
Amino acid synthesis is the set of biochemical processes by which the amino acids are produced. The substrates for these processes are various compounds in the organism's diet or growth media. Not all organisms are able to synthesize all amino acids. For example, humans can synthesize 11 of the 20 standard amino acids. These 11 are called the non-essential amino acids).
In enzymology, an aspartate-semialdehyde dehydrogenase is an enzyme that is very important in the biosynthesis of amino acids in prokaryotes, fungi, and some higher plants. It forms an early branch point in the metabolic pathway forming lysine, methionine, leucine and isoleucine from aspartate. This pathway also produces diaminopimelate which plays an essential role in bacterial cell wall formation. There is particular interest in ASADH as disabling this enzyme proves fatal to the organism giving rise to the possibility of a new class of antibiotics, fungicides, and herbicides aimed at inhibiting it.
In enzymology, a diaminopimelate dehydrogenase (EC 1.4.1.16) is an enzyme that catalyzes the chemical reaction
In enzymology, an alanine racemase is an enzyme that catalyzes the chemical reaction
In enzymology, an aspartate racemase is an enzyme that catalyzes the following chemical reaction:
In enzymology, glutamate racemase is an enzyme that catalyzes the chemical reaction
The enzyme diaminopimelate decarboxylase (EC 4.1.1.20) catalyzes the cleavage of carbon-carbon bonds in meso 2,6 diaminoheptanedioate to produce CO2 and L-lysine, the essential amino acid. It employs the cofactor pyridoxal phosphate, also known as PLP, which participates in numerous enzymatic transamination, decarboxylation and deamination reactions.
In enzymology, a N-acetyldiaminopimelate deacetylase (EC 3.5.1.47) is an enzyme that catalyzes the chemical reaction
In enzymology, a succinyl-diaminopimelate desuccinylase (EC 3.5.1.18) is an enzyme that catalyzes the chemical reaction
In enzymology, a L,L-diaminopimelate aminotransferase (EC 2.6.1.83) is an enzyme that catalyzes the chemical reaction
Diaminopimelic acid (DAP) is an amino acid, representing an epsilon-carboxy derivative of lysine.
Tabtoxin, also known as wildfire toxin, is a simple monobactam phytotoxin produced by Pseudomonas syringae. It is the precursor to the antibiotic tabtoxinine β-lactam (TBL). It is produced by:
The bacterial cell wall provides strength and rigidity to counteract internal osmotic pressure, and protection against the environment. The peptidoglycan layer gives the cell wall its strength, and helps maintain the overall shape of the cell. The basic peptidoglycan structure of both Gram-positive and Gram-negative bacteria comprises a sheet of glycan chains connected by short cross-linking polypeptides. Biosynthesis of peptidoglycan is a multi-step process comprising three main stages:
4-Hydroxy-tetrahydrodipicolinate synthase (EC 4.3.3.7, dihydrodipicolinate synthase, dihydropicolinate synthetase, dihydrodipicolinic acid synthase, L-aspartate-4-semialdehyde hydro-lyase (adding pyruvate and cyclizing), dapA (gene)) is an enzyme with the systematic name L-aspartate-4-semialdehyde hydro-lyase (adding pyruvate and cyclizing; (4S)-4-hydroxy-2,3,4,5-tetrahydro-(2S)-dipicolinate-forming). This enzyme catalyses the following chemical reaction
L-Aspartic-4-semialdehyde is an α-amino acid derivative of aspartate. It is an important intermediate in the aspartate pathway, which is a metabolic pathway present in bacteria and plants. The aspartate pathway leads to the biosynthesis of a variety of amino acids from aspartate, including lysine, methionine, and threonine.