Biology:Dihydrodipicolinate synthase
| 4-hydroxy-tetrahydrodipicolinate synthase | |||||||||
|---|---|---|---|---|---|---|---|---|---|
 Dihydrodipicolinate synthase homotetramer, Vitis vinifera | |||||||||
| Identifiers | |||||||||
| EC number | 4.3.3.7 | ||||||||
| CAS number | 9055-59-8 | ||||||||
| 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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| Dihydrodipicolinate synthetase family | |||||||||
|---|---|---|---|---|---|---|---|---|---|
 Crystal structure of dihydrodipicolinate synthase dapa-2 (ba3935) from Bacillus anthracis at 1.94a resolution. | |||||||||
| Identifiers | |||||||||
| Symbol | DHDPS | ||||||||
| Pfam | PF00701 | ||||||||
| Pfam clan | CL0036 | ||||||||
| InterPro | IPR002220 | ||||||||
| PROSITE | PDOC00569 | ||||||||
| SCOP2 | 1dhp / SCOPe / SUPFAM | ||||||||
| CDD | cd00950 | ||||||||
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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).[1][2][3][4] This enzyme catalyses the following chemical reaction
- pyruvate + L-aspartate-4-semialdehyde [math]\displaystyle{ \rightleftharpoons }[/math] (2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinate + H2O
The reaction proceeds in three consecutive steps.
Function
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 4.1.3.3) (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.
Structure
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 α/β-barrel, and a C-terminal α-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.
References
- ↑ "The condensation step in diaminopimelate synthesis". The Journal of Biological Chemistry 240 (12): 4710–6. Dec 1965. doi:10.1016/S0021-9258(18)97013-4. PMID 5321309.
- ↑ "Reaction mechanism of Escherichia coli dihydrodipicolinate synthase investigated by X-ray crystallography and NMR spectroscopy". Biochemistry 36 (1): 24–33. Jan 1997. doi:10.1021/bi962272d. PMID 8993314.
- ↑ "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. Jun 2010. doi:10.1021/jm100349s. PMID 20503968.
- ↑ "How essential is the 'essential' active-site lysine in dihydrodipicolinate synthase?". Biochimie 92 (7): 837–45. Jul 2010. doi:10.1016/j.biochi.2010.03.004. PMID 20353808.
- ↑ 5.0 5.1 "The crystal structure of dihydrodipicolinate synthase from Escherichia coli at 2.5 A resolution". Journal of Molecular Biology 246 (1): 227–39. Feb 1995. doi:10.1006/jmbi.1994.0078. PMID 7853400.
- ↑ "The Rhizobium meliloti rhizopine mos locus is a mosaic structure facilitating its symbiotic regulation". Journal of Bacteriology 175 (16): 5193–204. Aug 1993. doi:10.1128/jb.175.16.5193-5204.1993. PMID 8349559.
Further reading
- "The pyruvate-aspartic semialdehyde condensing enzyme of Escherichia coli". The Journal of Biological Chemistry 245 (6): 1362–73. Mar 1970. doi:10.1016/S0021-9258(18)63245-4. PMID 4910051.
External links
- 4-hydroxy-tetrahydrodipicolinate+synthase at the US National Library of Medicine Medical Subject Headings (MeSH)
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