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706  structures 8245  species 0  interactions 25699  sequences 106  architectures

Family: DHDPS (PF00701)

Summary: Dihydrodipicolinate synthetase family

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This is the Wikipedia entry entitled "Dihydrodipicolinate synthase". More...

Dihydrodipicolinate synthase Edit Wikipedia article

4-hydroxy-tetrahydrodipicolinate synthase
EC number4.3.3.7
CAS number9055-59-8
IntEnzIntEnz view
ExPASyNiceZyme view
MetaCycmetabolic pathway
PDB structuresRCSB PDB PDBe PDBsum
Gene OntologyAmiGO / QuickGO
Dihydrodipicolinate synthetase family
PDB 1xky EBI.jpg
Crystal structure of dihydrodipicolinate synthase dapa-2 (ba3935) from Bacillus anthracis at 1.94a resolution.
Pfam clanCL0036

4-Hydroxy-tetrahydrodipicolinate synthase (EC, 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).[1][2][3][4] This enzyme catalyses the following chemical reaction

pyruvate + L-aspartate-4-semialdehyde (2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinate + H2O

The reaction proceeds in three consecutive steps.


This enzyme belongs to the family of lyases, specifically the amine-lyases, which cleave carbon-nitrogen bonds. 4-hydroxy-tetrahydrodipicolinate synthase is the key enzyme in lysine biosynthesis via the diaminopimelate pathway of prokaryotes, some phycomycetes, and higher plants. The enzyme catalyses the condensation of L-aspartate-beta-semialdehyde and pyruvate to 4-hydroxy-tetrahydropicolinic acid via a ping-pong mechanism in which pyruvate binds to the enzyme by forming a Schiff base with a lysine residue.[5]

Related enzymes

Three other proteins are structurally related to this enzyme and probably also act via a similar catalytic mechanism. These are Escherichia coli N-acetylneuraminate lyase (EC (protein NanA), which catalyses the condensation of N-acetyl-D-mannosamine and pyruvate to form N-acetylneuraminate; Rhizobium meliloti (Sinorhizobium meliloti) protein MosA,[6] which is involved in the biosynthesis of the rhizopine 3-O-methyl-scyllo-inosamine; and E. coli hypothetical protein YjhH.


The sequences of 4-hydroxy-tetrahydrodipicolinate synthase from different sources are well-conserved. The structure takes the form of a homotetramer, in which 2 monomers are related by an approximate 2-fold symmetry.[5] Each monomer comprises 2 domains: an 8-fold alpha-/beta-barrel, and a C-terminal alpha-helical domain. The fold resembles that of N-acetylneuraminate lyase. The active site lysine is located in the barrel domain, and has access via 2 channels on the C-terminal side of the barrel.


  1. ^ Yugari Y, Gilvarg C (Dec 1965). "The condensation step in diaminopimelate synthesis". The Journal of Biological Chemistry. 240 (12): 4710–6. PMID 5321309.
  2. ^ Blickling S, Renner C, Laber B, Pohlenz HD, Holak TA, Huber R (Jan 1997). "Reaction mechanism of Escherichia coli dihydrodipicolinate synthase investigated by X-ray crystallography and NMR spectroscopy". Biochemistry. 36 (1): 24–33. doi:10.1021/bi962272d. PMID 8993314.
  3. ^ Devenish SR, Blunt JW, Gerrard JA (Jun 2010). "NMR studies uncover alternate substrates for dihydrodipicolinate synthase and suggest that dihydrodipicolinate reductase is also a dehydratase". Journal of Medicinal Chemistry. 53 (12): 4808–12. doi:10.1021/jm100349s. PMID 20503968.
  4. ^ Soares da Costa TP, Muscroft-Taylor AC, Dobson RC, Devenish SR, Jameson GB, Gerrard JA (Jul 2010). "How essential is the 'essential' active-site lysine in dihydrodipicolinate synthase?". Biochimie. 92 (7): 837–45. doi:10.1016/j.biochi.2010.03.004. PMID 20353808.
  5. ^ a b Mirwaldt C, Korndörfer I, Huber R (Feb 1995). "The crystal structure of dihydrodipicolinate synthase from Escherichia coli at 2.5 A resolution". Journal of Molecular Biology. 246 (1): 227–39. doi:10.1006/jmbi.1994.0078. PMID 7853400.
  6. ^ Murphy PJ, Trenz SP, Grzemski W, De Bruijn FJ, Schell J (Aug 1993). "The Rhizobium meliloti rhizopine mos locus is a mosaic structure facilitating its symbiotic regulation". Journal of Bacteriology. 175 (16): 5193–204. PMC 204987. PMID 8349559.

Further reading

  • Shedlarski JG, Gilvarg C (Mar 1970). "The pyruvate-aspartic semialdehyde condensing enzyme of Escherichia coli". The Journal of Biological Chemistry. 245 (6): 1362–73. PMID 4910051.

External links

This article incorporates text from the public domain Pfam and InterPro: IPR002220

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.

Dihydrodipicolinate synthetase family Provide feedback

This family has a TIM barrel structure.

Literature references

  1. Izard T, Lawrence MC, Malby RL, Lilley GG, Colman PM; , Structure 1994;2:361-369.: The three-dimensional structure of N-acetylneuraminate lyase from Escherichia coli. PUBMED:8081752 EPMC:8081752

Internal database links

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR002220

Dihydrodipicolinate synthase (EC (DHDPS, DapA) catalyses, in higher plants, some fungi and bacteria (gene dapA), the first reaction specific to the biosynthesis of lysine and of diaminopimelate [ PUBMED:22949190 ]. DHDPS is responsible for the condensation of aspartate semialdehyde and pyruvate by a ping-pong mechanism in which pyruvate first binds to the enzyme by forming a Schiff-base with a lysine residue [ PUBMED:1463470 , PUBMED:20025926 ].

Other proteins are structurally related to DHDPS and probably also act via a similar catalytic mechanism [ PUBMED:9047371 ]:

  • Escherichia coli N-acetylneuraminate lyase (EC (gene nanA), which catalyses the condensation of N-acetyl-D-mannosamine and pyruvate to form N-acetylneuraminate.
  • Trans-o-hydroxybenzylidenepyruvate hydratase-aldolase.
  • D-4-deoxy-5-oxoglucarate dehydratase.
  • Rhizobium meliloti protein mosA [ PUBMED:8349559 ], which is involved in the biosynthesis of the rhizopine 3-o-methyl-scyllo-inosamine.
  • Thermoproteus tenax 2-dehydro-3-deoxy-D-gluconate/2-dehydro-3-deoxy-phosphogluconate aldolase (KdgA) [ PUBMED:18186475 ].

Gene Ontology

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Domain organisation

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Seed source: Pfam-B_557 (release 2.1)
Previous IDs: none
Type: Domain
Sequence Ontology: SO:0000417
Author: Bateman A , Griffiths-Jones SR
Number in seed: 9
Number in full: 25699
Average length of the domain: 281.00 aa
Average identity of full alignment: 25 %
Average coverage of the sequence by the domain: 92.41 %

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HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 61295632 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 22.1 22.1
Trusted cut-off 22.1 22.1
Noise cut-off 22.0 22.0
Model length: 289
Family (HMM) version: 25
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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 DHDPS domain has been found. There are 706 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 sequence.

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