Dihydrodipicolinate synthase

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). This enzyme catalyses the following chemical reaction

pyruvate + L-aspartate-4-semialdehyde

\rightleftharpoons

(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.

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, 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. 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

Yugari Y, Gilvarg C (Dec 1965). "The condensation step in diaminopimelate synthesis". The Journal of Biological Chemistry. 240 (12): 4710–6. doi:10.1016/S0021-9258(18)97013-4. PMID 5321309.
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.
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.
^ 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.
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.

External links

4-hydroxy-tetrahydrodipicolinate+synthase at the U.S. National Library of Medicine Medical Subject Headings (MeSH)

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

v t e Carbon–nitrogen lyases (EC 4.3)
4.3.1: ammonia-lyases	Histidine ammonia-lyase Formiminotransferase cyclodeaminase Serine dehydratase Phenylalanine ammonia-lyase
4.3.2: amidine-lyases	Argininosuccinate lyase Adenylosuccinate lyase

v t e Enzymes
Activity	Active site Binding site Catalytic triad Oxyanion hole Enzyme promiscuity Diffusion-limited enzyme Cofactor Enzyme catalysis
Regulation	Allosteric regulation Cooperativity Enzyme inhibitor Enzyme activator
Classification	EC number Enzyme superfamily Enzyme family List of enzymes
Kinetics	Enzyme kinetics Eadie–Hofstee diagram Hanes–Woolf plot Lineweaver–Burk plot Michaelis–Menten kinetics
Types	EC1 Oxidoreductases (list) EC2 Transferases (list) EC3 Hydrolases (list) EC4 Lyases (list) EC5 Isomerases (list) EC6 Ligases (list) EC7 Translocases (list)

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