|PDB structures||RCSB PDB PDBe PDBsum|
|Gene Ontology||AmiGO / QuickGO|
|Dihydrodipicolinate synthetase family|
|SCOP2||1dhp / SCOPe / SUPFAM|
4-Hydroxy-tetrahydrodipicolinate synthase (EC 184.108.40.206, 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
- 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.
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 220.127.116.11) (protein NanA), which catalyses the condensation of N-acetyl-D-mannosamine and pyruvate to form N-acetylneuraminate; Rhizobium meliloti (Sinorhizobium meliloti) protein MosA, 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. 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.
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- 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.
- 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.
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- 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. doi:10.1128/jb.175.16.5193-5204.1993. PMC 204987. PMID 8349559.
- 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.