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42  structures 3504  species 1  interaction 7321  sequences 6  architectures

Family: DAP_epimerase (PF01678)

Summary: Diaminopimelate epimerase

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This is the Wikipedia entry entitled "Diaminopimelate epimerase". More...

Diaminopimelate epimerase Edit Wikipedia article

diaminopimelate epimerase
Identifiers
EC number 5.1.1.7
CAS number 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 / EGO
Diaminopimelate epimerase
Identifiers
Symbol DAP_epimerase
Pfam PF01678
InterPro IPR001653
PROSITE PDOC01029

In enzymology, a diaminopimelate epimerase (EC 5.1.1.7) is an enzyme that catalyzes the chemical reaction

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 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.

Background[edit]

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 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. For more information see.[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, utilises 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. It 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 homologus in structure though they share little sequence similarity.[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 catalytic reaction.[5] Other PLP-independent racemases such as glutamate racemase have been shown to share a similar structure and mechanism of catalysis.

Structural studies[edit]

As of late 2007, 4 structures have been solved for this class of enzymes, with PDB accession codes 1BWZ, 1GQZ, 2GKE, and 2GKJ.

References[edit]

  1. ^ Viola RE (2001). "The central enzymes of the aspartate family of amino acid biosynthesis". Acc. Chem. Res. 34 (5): 339–49. doi:10.1021/ar000057q. PMID 11352712. 
  2. ^ Blanchard JS, Born TL (1999). "Structure/function studies on enzymes in the diaminopimelate pathway of bacterial cell wall biosynthesis". Curr Opin Chem Biol 3 (5): 607–13. PMID 10508663. 
  3. ^ Leustek T, Hudson AO, Bless C, Macedo P, Chatterjee SP, Singh BK, Gilvarg C (2005). "Biosynthesis of lysine in plants: evidence for a variant of the known bacterial pathways". Biochim. Biophys. Acta 1721 (1): 27–36. doi:10.1016/j.bbagen.2004.09.008. PMID 15652176. 
  4. ^ Scapin G, Blanchard JS, Cirilli M, Zheng R (1998). "Structural symmetry: the three-dimensional structure of Haemophilus influenzae diaminopimelate epimerase". Biochemistry 37 (47): 16452–16458. doi:10.1021/bi982138o. PMID 9843410. 
  5. ^ Roper DI, Huyton T, Lloyd AJ, Turkenburg J (2004). "Refinement of Haemophilus influenzae diaminopimelic acid epimerase (DapF) at 1.75 A resolution suggests a mechanism for stereocontrol during catalysis". Acta Crystallogr. D 60 (Pt 2): 397–400. doi:10.1107/S0907444903027999. PMID 14747737. 

Further reading[edit]

This article incorporates text from the public domain Pfam and InterPro IPR001653

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.

Diaminopimelate epimerase Provide feedback

Diaminopimelate epimerase contains two domains of the same alpha/beta fold, both contained in this family.

Literature references

  1. Cirilli M, Zheng R, Scapin G, Blanchard JS; , Biochemistry 1998;37:16452-16458.: Structural symmetry: the three-dimensional structure of Haemophilus influenzae diaminopimelate epimerase. PUBMED:9843410 EPMC:9843410


External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR001653

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 [PUBMED:11352712].

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 [PUBMED:20418392].

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 [PUBMED:20418392].

  • 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 (EC), 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 30 kDa consisting of two domains which are homologus in structure though they share little sequence similarity [PUBMED:9843410]. 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 catalytic reaction [PUBMED:14747737]. Other PLP-independent racemases such as glutamate racemase have been shown to share a similar structure and mechanism of catalysis.

Gene Ontology

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Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

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Pfam Clan

This family is a member of clan DAP_epimerase (CL0288), which has the following description:

This superfamily includes DAP epimerase and proline racemase as well as the PrpF protein. It has been suggested that this fold may have evolved from the HotDog fold [1].

The clan contains the following 4 members:

DAP_epimerase PhzC-PhzF Pro_racemase PrpF

Alignments

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(5624)
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(4219)
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(1251)
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  Seed
(28)
Full
(7321)
Representative proteomes NCBI
(5624)
Meta
(4219)
RP15
(612)
RP35
(1251)
RP55
(1586)
RP75
(1855)
Alignment:
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  Seed
(28)
Full
(7321)
Representative proteomes NCBI
(5624)
Meta
(4219)
RP15
(612)
RP35
(1251)
RP55
(1586)
RP75
(1855)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download   Download  
Gzipped Download   Download   Download   Download   Download   Download   Download   Download  

You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

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Curation and family details

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Curation View help on the curation process

Seed source: Pfam-B_2089 (release 4.1)
Previous IDs: none
Type: Domain
Author: Bateman A, Griffiths-Jones SR
Number in seed: 28
Number in full: 7321
Average length of the domain: 119.90 aa
Average identity of full alignment: 25 %
Average coverage of the sequence by the domain: 83.62 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 20.7 20.7
Trusted cut-off 20.7 20.7
Noise cut-off 20.6 20.6
Model length: 121
Family (HMM) version: 14
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Species distribution

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Interactions

There is 1 interaction for this family. More...

DAP_epimerase

Structures

For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the DAP_epimerase domain has been found. There are 42 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein seqence.

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