enzymology Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. A ...

, a diaminopimelate epimerase () is an

enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. A ...

that

catalyzes Catalysis () is the process of increasing the rate of a chemical reaction by adding a substance known as a catalyst (). Catalysts are not consumed in the reaction and remain unchanged after it. If the reaction is rapid and the catalyst recyc ...

the

chemical reaction A chemical reaction is a process that leads to the IUPAC nomenclature for organic transformations, chemical transformation of one set of chemical substances to another. Classically, chemical reactions encompass changes that only involve the pos ...

:LL-2,6-diaminoheptanedioate

\rightleftharpoons

meso-diaminoheptanedioate 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

racemase Epimerases and racemases are isomerase enzymes that catalyze the inversion of stereochemistry in biological molecules. Racemases catalyze the stereochemical inversion around the asymmetric carbon atom in a substrate having only one center of asymm ...

s and

epimerase Epimerases and racemases are isomerase enzymes that catalyze the inversion of stereochemistry in biological molecules. Racemases catalyze the stereochemical inversion around the asymmetric carbon atom in a substrate having only one center of asymme ...

s acting on

amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha am ...

s and derivatives. The systematic name of this enzyme class is LL-2,6-diaminoheptanedioate 2-epimerase. This enzyme participates in

lysine biosynthesis 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 form under biological conditions), an α-carboxylic acid group (which is in the deprotonated −CO ...

Background

Bacteria, plants and fungi

metabolise Metabolism (, from el, μεταβολή ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cell ...

aspartic acid Aspartic acid (symbol Asp or D; the ionic form is known as aspartate), is an α-amino acid that is used in the biosynthesis of proteins. Like all other amino acids, it contains an amino group and a carboxylic acid. Its α-amino group is in the pro ...

to produce four

amino acids Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha am ...

lysine 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 form under biological conditions), an α-carboxylic acid group (which is in the deprotonated −C ...

threonine Threonine (symbol Thr or T) is an amino acid that is used in the biosynthesis of proteins. It contains an α-amino group (which is in the protonated −NH form under biological conditions), a carboxyl group (which is in the deprotonated −COO� ...

methionine Methionine (symbol Met or M) () is an essential amino acid in humans. As the precursor of other amino acids such as cysteine and taurine, versatile compounds such as SAM-e, and the important antioxidant glutathione, methionine plays a critical ro ...

and

isoleucine Isoleucine (symbol Ile or I) is an α-amino acid that is used in the biosynthesis of proteins. It contains an α-amino group (which is in the protonated −NH form under biological conditions), an α-carboxylic acid group (which is in the deprot ...

- in a series of reactions known as the aspartate pathway. Additionally, several important

metabolic intermediate Metabolic intermediates are molecules that are the precursors or metabolites of biologically significant molecules. Although these intermediates are of relatively minor direct importance to cellular function, they can play important roles in the a ...

s are produced by these reactions, such as

diaminopimelic acid Diaminopimelic acid (DAP) is an amino acid, representing an epsilon-carboxy derivative of lysine. DAP is a characteristic of certain cell walls of some bacteria. DAP is often found in the peptide linkages of NAM-NAG chains that make up the ce ...

, an essential component of bacterial cell wall

biosynthesis 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. ...

, and

dipicolinic acid Dipicolinic acid (pyridine-2,6-dicarboxylic acid or PDC and DPA) is a chemical compound which plays a role in the heat resistance of bacterial endospores. It is also used to prepare dipicolinato ligated lanthanide and transition metal complexes f ...

, which is involved in sporulation (spore production) in

Gram-positive bacteria In bacteriology, gram-positive bacteria are bacteria that give a positive result in the Gram stain test, which is traditionally used to quickly classify bacteria into two broad categories according to their type of cell wall. Gram-positive bact ...

. Members of the animal kingdom do not possess this pathway and must therefore acquire these essential

through their diet. Research into improving the

metabolic flux Flux, or metabolic flux is the rate of turnover of molecules through a metabolic pathway. Flux is regulated by the enzymes involved in a pathway. Within cells, regulation of flux is vital for all metabolic pathways to regulate the pathway's activ ...

through this pathway has the potential to increase the yield of the essential

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. The

branch of the aspartate pathway produces the essential amino acid

via the intermediate

meso Meso or mesos may refer to: * Apache Mesos, a computer clustering management platform * Meso, in-game currency for the massively multiplayer online role-playing game '' MapleStory'' * Meso compound, a stereochemical classification in chemistry * ...

(meso-DAP), which is also a vital cell wall component in

Gram-negative Gram-negative bacteria are bacteria that do not retain the crystal violet stain used in the Gram staining method of bacterial differentiation. They are characterized by their cell envelopes, which are composed of a thin peptidoglycan cell wall ...

bacteria. The production of dihydropicolinate from aspartate-semialdehyde controls flux into the

pathway. Three variants of this pathway exist, differing in how tetrahydropicolinate (formed by reduction of dihydropicolinate) is

metabolised Metabolism (, from el, μεταβολή ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cell ...

to meso-DAP. One variant, the most commonly found one in

archaea Archaea ( ; singular archaeon ) is a domain of single-celled organisms. These microorganisms lack cell nuclei and are therefore prokaryotes. Archaea were initially classified as bacteria, receiving the name archaebacteria (in the Archaebac ...

and bacteria, uses primarily

succinyl Succinic acid () is a dicarboxylic acid with the chemical formula (CH2)2(CO2H)2. The name derives from Latin ''succinum'', meaning amber. In living organisms, succinic acid takes the form of an anion, succinate, which has multiple biological ro ...

intermediates, while a second variant, found only in Bacillus, utilizes primarily

acetyl In organic chemistry, acetyl is a functional group with the chemical formula and the structure . It is sometimes represented by the symbol Ac (not to be confused with the element actinium). In IUPAC nomenclature, acetyl is called ethanoyl, ...

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

by a decarboxylase, or, in

bacteria, assimilated into the cell wall. Evidence exists that a fourth, currently unknown, variant of this pathway may function in plants.

Diaminopimelate Diaminopimelic acid (DAP) is an amino acid, representing an epsilon-carboxy derivative of lysine. DAP is a characteristic of certain cell walls of some bacteria. DAP is often found in the peptide linkages of NAM-NAG chains that make up the cell ...

(), which catalyses the

isomerisation In chemistry, isomerization or isomerisation is the process in which a molecule, polyatomic ion or molecular fragment is transformed into an isomer with a different chemical structure. Enolization is an example of isomerization, as is tautomeriz ...

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 In bioinformatics, a sequence alignment is a way of arranging the sequences of DNA, RNA, or protein to identify regions of similarity that may be a consequence of functional, structural, or evolutionary relationships between the sequences. Alig ...

. Each domain consists of mixed beta-sheets which fold into a barrel around the central helix. The

active site In biology and biochemistry, the active site is the region of an enzyme where substrate molecules bind and undergo a chemical reaction. The active site consists of amino acid residues that form temporary bonds with the substrate (binding site) a ...

cleft is formed from both domains and contains two conserved

cysteine Cysteine (symbol Cys or C; ) is a semiessential proteinogenic amino acid with the formula . The thiol side chain in cysteine often participates in enzymatic reactions as a nucleophile. When present as a deprotonated catalytic residue, sometime ...

s thought to function as the acid and base in the

Catalysis Catalysis () is the process of increasing the rate of a chemical reaction by adding a substance known as a catalyst (). Catalysts are not consumed in the reaction and remain unchanged after it. If the reaction is rapid and the catalyst recyc ...

. Other PLP-independent racemases such as

glutamate racemase In enzymology, glutamate racemase (MurI with a capital ''i'') () is an enzyme that catalysis, catalyzes the chemical reaction :L-glutamate \rightleftharpoons D-glutamate Hence, this enzyme RacE has one substrate (biochemistry), substrate, glutam ...

have been shown to share a similar structure and mechanism of

catalysis Catalysis () is the process of increasing the rate of a chemical reaction by adding a substance known as a catalyst (). Catalysts are not consumed in the reaction and remain unchanged after it. If the reaction is rapid and the catalyst recyc ...

Structural studies

As of late 2007, 4 structures have been solved for this class of enzymes, with PDB accession codes , , , and .

Background

Structural studies

References

Further reading