Letunic et al. (2017) Nucleic Acids Res doi: 10.1093/nar/gkx922
Letunic et al. (2020) Nucleic Acids Res doi: 10.1093/nar/gkaa937

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DHDPS Dihydrodipicolinate synthetase family

SMART accession number:	SM01130
Description:	This family has a TIM barrel structure. This enzyme belongs to the family of lyases, specifically the hydro-lyases, which cleave carbon-oxygen bonds.
Interpro abstract (IPR002220):	Dihydrodipicolinate synthase (EC 4.2.1.52) (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 4.1.3.3) (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) ].
GO function:	lyase activity (GO:0016829)
Family alignment:	View or CHROMA formatHMM/Web logoCLUSTALW formatMSF formatFASTA formatPIR format

There are 57397 DHDPS domains in 57392 proteins in SMART's nrdb database.

Click on the following links for more information.

• Evolution (species in which this domain is found)

• Taxonomic distribution of proteins containing DHDPS domain.

  This tree includes only several representative species. The complete taxonomic breakdown of all proteins with DHDPS domain is also avaliable.

  Click on the protein counts, or double click on taxonomic names to display all proteins containing DHDPS domain in the selected taxonomic class.

• Cellular role (predicted cellular role)

• Cellular role: metabolism
  

• Literature (relevant references for this domain)

• Primary literature is listed below; Automatically-derived, secondary literature is also avaliable.

  • Izard T, Lawrence MC, Malby RL, Lilley GG, Colman PM
  • The three-dimensional structure of N-acetylneuraminate lyase from Escherichiacoli.
  • Structure. 1994; 2: 361-9
  • Display abstract

  • BACKGROUND: N-acetylneuraminate lyase catalyzes the cleavage ofN-acetylneuraminic acid (sialic acid) to form pyruvate andN-acetyl-D-mannosamine. The enzyme plays an important role in the regulation ofsialic acid metabolism in bacteria. The reverse reaction can be exploited for thesynthesis of sialic acid and some of its derivatives. RESULTS: The structure ofthe enzyme from Escherichia coli has been determined to 2.2 A resolution by X-raycrystallography. The enzyme is shown to be a tetramer, in which each subunitconsists of an alpha/beta-barrel domain followed by a carboxy-terminal extension of three alpha-helices. CONCLUSIONS: The active site of the enzyme is tentativelyidentified as a pocket at the carboxy-terminal end of the eight-strandedbeta-barrel. Lys165 lies within this pocket and is probably the reactive residue which forms a Schiff base intermediate with the substrate. The sequence ofN-acetylneuraminate lyase has similarities to those of dihydrodipicolinatesynthase and MosA (an enzyme implicated in rhizopine synthesis) suggesting thatthese last two enzymes share a similar structure to N-acetylneuraminate lyase.

• Structure (3D structures containing this domain)

• 3D Structures of DHDPS domains in PDB

  PDB code	Main view	Title
  1dhp		DIHYDRODIPICOLINATE SYNTHASE
  1f5z		CRYSTAL STRUCTURE ANALYSIS OF N-ACETYLNEURAMINATE LYASE FROM HAEMOPHILUS INFLUENZAE: CRYSTAL FORM I
  1f6k		CRYSTAL STRUCTURE ANALYSIS OF N-ACETYLNEURAMINATE LYASE FROM HAEMOPHILUS INFLUENZAE: CRYSTAL FORM II
  1f6p		CRYSTAL STRUCTURE ANALYSIS OF N-ACETYLNEURAMINATE LYASE FROM HAEMOPHILUS INFLUENZAE: CRYSTAL FORM III
  1f73		CRYSTAL STRUCTURE ANALYSIS OF N-ACETYLNEURAMINATE LYASE FROM HAEMOPHILUS INFLUENZAE: CRYSTAL FORM III IN COMPLEX WITH SIALIC ACID ALDITOL
  1f74		CRYSTAL STRUCTURE ANALYSIS OF N-ACETYLNEURAMINATE LYASE FROM HAEMOPHILUS INFLUENZAE: CRYSTAL FORM II COMPLEXED WITH 4-DEOXY-SIALIC ACID
  1f7b		CRYSTAL STRUCTURE ANALYSIS OF N-ACETYLNEURAMINATE LYASE FROM HAEMOPHILUS INFLUENZAE: CRYSTAL FORM II IN COMPLEX WITH 4-OXO-SIALIC ACID
  1fdy		N-ACETYLNEURAMINATE LYASE IN COMPLEX WITH HYDROXYPYRUVATE
  1fdz		N-ACETYLNEURAMINATE LYASE IN COMPLEX WITH PYRUVATE VIA BOROHYDRIDE REDUCTION
  1hl2		Crystal structure of N-acetylneuraminate lyase from E. coli mutant L142R in complex with b-hydroxypyruvate
  1nal		THE THREE-DIMENSIONAL STRUCTURE OF N-ACETYLNEURAMINATE LYASE FROM ESCHERICHIA COLI
  1o5k		Crystal structure of Dihydrodipicolinate synthase (TM1521) from Thermotoga maritima at 1.80 A resolution
  1s5t		Crystal Structure Analysis of a mutant of DIHYDRODIPICOLINATE SYNTHASE--residue thr44 to val44
  1s5v		Crystal Structure Analysis of a mutant of DIHYDRODIPICOLINATE SYNTHASE--residue Tyr107 to Phe107
  1s5w		Crystal Structure Analysis of a mutant of DIHYDRODIPICOLINATE SYNTHASE--residue Tyr133 to Phe133
  1w37		2-keto-3-deoxygluconate(KDG) aldolase of Sulfolobus solfataricus
  1w3i		Sulfolobus solfataricus 2-keto-3-deoxygluconate (KDG) aldolase complex with pyruvate
  1w3n		Sulfolobus solfataricus 2-keto-3-deoxygluconate (KDG) aldolase complex with D-KDG
  1w3t		Sulfolobus solfataricus 2-keto-3-deoxygluconate (KDG) aldolase complex with D-KDGal, D-Glyceraldehyde and pyruvate
  1xky		Crystal Structure of Dihydrodipicolinate Synthase DapA-2 (BA3935) from Bacillus Anthracis at 1.94A Resolution.
  1xl9		Crystal Structure of Dihydrodipicolinate Synthase DapA-2 (BA3935) from Bacillus Anthracis.
  1xxx		Crystal structure of Dihydrodipicolinate Synthase (DapA, Rv2753c) from Mycobacterium tuberculosis
  1yxc		Structure of E. coli dihydrodipicolinate synthase to 1.9 A
  1yxd		Structure of E. coli dihydrodipicolinate synthase bound with allosteric inhibitor (S)-lysine to 2.0 A
  2a6l		Dihydrodipicolinate synthase (E. coli)- mutant R138H
  2a6n		Dihydrodipicolinate synthase (E. coli)- mutant R138A
  2ats		Dihydrodipicolinate synthase co-crystallised with (S)-lysine
  2ehh		Crystal structure of dihydrodipicolinate synthase from aquifex aeolicus
  2hmc		The Crystal Structure of Dihydrodipicolinate Synthase DapA from Agrobacterium tumefaciens
  2nuw		2-keto-3-deoxygluconate aldolase from Sulfolobus acidocaldarius, native structure at 1.8 A resolution
  2nux		2-keto-3-deoxygluconate aldolase from Sulfolobus acidocaldarius, native structure in p6522 at 2.5 A resolution
  2nuy		2-keto-3-deoxygluconate aldolase from Sulfolobus acidocaldarius in complex with pyruvate
  2ojp		The crystal structure of a dimeric mutant of Dihydrodipicolinate synthase from E.coli- DHDPS-L197Y
  2pcq		Crystal structure of putative dihidrodipicolinate synthase (TTHA0737) from Thermus Thermophilus HB8
  2pur		Structure of dihydrodipicolinate synthase mutant Thr44Ser at 1.7 A.
  2r8w		The crystal structure of dihydrodipicolinate synthase (Atu0899) from Agrobacterium tumefaciens str. C58
  2r91		Crystal Structure of KD(P)GA from T.tenax
  2r94		Crystal Structure of KD(P)GA from T.tenax
  2rfg		Crystal structure of dihydrodipicolinate synthase from Hahella chejuensis at 1.5A resolution
  2v8z		Crystal Structure of YagE, a prophage protein belonging to the dihydrodipicolinic acid synthase family from E. coli K12
  2v9d		Crystal Structure of YagE, a prophage protein belonging to the dihydrodipicolinic acid synthase family from E. coli K12
  2vc6		Structure of MosA from S. meliloti with pyruvate bound
  2wkj		Crystal structure of the E192N mutant of E. Coli N-acetylneuraminic acid lyase in complex with pyruvate at 1.45A resolution in space group P212121
  2wnn		Structure of wild type E. coli N-acetylneuraminic acid lyase in complex with pyruvate in space group P21
  2wnq		Structure of the E192N mutant of E. coli N-acetylneuraminic acid lyase in space group P21
  2wnz		Structure of the E192N mutant of E. coli N-acetylneuraminic acid lyase in complex with pyruvate in space group P21 crystal form I
  2wo5		Structure of wild type E. coli N-acetylneuraminic acid lyase in space group P21 crystal form I
  2wpb		Crystal structure of the E192N mutant of E. Coli N-acetylneuraminic acid lyase in complex with pyruvate and the inhibitor (2R,3R)-2,3,4- trihydroxy-N,N-dipropylbutanamide in space group P21 crystal form I
  2xfw		Structure of the E192N mutant of E. coli N-acetylneuraminic acid lyase in complex with pyruvate in crystal form III
  2yda		Sulfolobus sulfataricus 2-keto-3-deoxygluconate aldolase Y103F,Y130F, A198F variant
  2ygy		Structure of wild type E. coli N-acetylneuraminic acid lyase in space group P21 crystal form II
  2yxg		Crystal structure of Dihyrodipicolinate Synthase (dapA)
  3a5f		High-resolution structure of DHDPS from Clostridium botulinum in complex with pyruvate
  3b4u		Crystal structure of dihydrodipicolinate synthase from Agrobacterium tumefaciens str. C58
  3c0j		Structure of E. coli dihydrodipicolinate synthase complexed with hydroxypyruvate
  3cpr		The crystal structure of Corynebacterium glutamicum dihydrodipicolinate synthase to 2.2 A resolution
  3d0c		Crystal structure of dihydrodipicolinate synthase from Oceanobacillus iheyensis at 1.9 A resolution
  3daq		Crystal structure of dihydrodipicolinate synthase from methicillin-resistant Staphylococcus aureus
  3den		Structure of E. coli DHDPS mutant Y107W
  3di0		Crystal Structure of Dihydrodipicolinate synthase from Staphylococcus aureus
  3di1		Crystal structure of the Staphylococcus aureus Dihydrodipicolinate synthase-pyruvate complex
  3du0		E. coli dihydrodipicolinate synthase with first substrate, pyruvate, bound in active site
  3dz1		Crystal structure of Dihydrodipicolinate Synthase from Rhodopseudomonas palustris at 1.87A resolution
  3e96		Crystal structure of dihydrodipicolinate synthase from bacillus clausii
  3eb2		Crystal structure of Dihydrodipicolinate Synthase from Rhodopseudomonas palustris at 2.0A resolution
  3fkk		Structure of L-2-keto-3-deoxyarabonate dehydratase
  3fkr		Structure of L-2-keto-3-deoxyarabonate dehydratase complex with pyruvate
  3flu		Crystal structure of dihydrodipicolinate synthase from the pathogen Neisseria meningitidis
  3g0s		Dihydrodipicolinate synthase from Salmonella typhimurium LT2
  3hij		Crystal structure of dihydrodipicolinate synthase from Bacillus anthracis in complex with its substrate, pyruvate
  3i7q		Dihydrodipicolinate synthase mutant - K161A
  3i7r		Dihydrodipicolinate synthase - K161R
  3i7s		Dihydrodipicolinate synthase mutant - K161A - with the substrate pyruvate bound in the active site.
  3ird		Structure of dihydrodipicolinate synthase from Clostridium botulinum
  3l21		The crystal structure of a dimeric mutant of dihydrodipicolinate synthase (DAPA, RV2753C) from Mycobacterium Tuberculosis - DHDPS-A204R
  3lbc		D-sialic acid aldolase complexed with L-arabinose
  3lbm		D-sialic acid aldolase
  3lcf		The D-sialic acid aldolase mutant V251I
  3lcg		The D-sialic acid aldolase mutant V251L
  3lch		The D-sialic acid aldolase mutant V251R
  3lci		The D-sialic acid aldolase mutant V251W
  3lcl		The D-sialic acid aldolase mutant V251I/V265I
  3lcw		L-KDO aldolase complexed with hydroxypyruvate
  3lcx		L-KDO aldolase
  3ler		Crystal Structure of Dihydrodipicolinate Synthase from Campylobacter jejuni subsp. jejuni NCTC 11168
  3m5v		Crystal Structure of Dihydrodipicolinate Synthase from Campylobacter jejuni
  3n2x		Crystal structure of YagE, a prophage protein belonging to the dihydrodipicolinic acid synthase family from E. coli K12 in complex with pyruvate
  3na8		Crystal Structure of a putative dihydrodipicolinate synthetase from Pseudomonas aeruginosa
  3nev		Crystal structure of YagE, a prophage protein from E. coli K12 in complex with KDGal
  3noe		Crystal Structure of Dihydrodipicolinate synthase from Pseudomonas aeruginosa
  3pb0		Characterisation of the first monomeric dihydrodipicolinate synthase variant reveals evolutionary insights
  3pb2		Characterisation of the first monomeric dihydrodipicolinate synthase variant reveals evolutionary insights
  3ps7		Biochemical studies and crystal structure determination of dihydrodipicolinate synthase from Pseudomonas aeruginosa
  3pud		Crystal structure of Dhydrodipicolinate synthase from Acinetobacter baumannii at 2.8A resolution
  3pue		Crystal structure of the complex of Dhydrodipicolinate synthase from Acinetobacter baumannii with lysine at 2.6A resolution
  3pul		Crystal structure of the complex of Dhydrodipicolinate synthase from Acinetobacter baumannii with lysine at 2.3A resolution
  3puo		Crystal structure of dihydrodipicolinate synthase from Pseudomonas aeruginosa(PsDHDPS)complexed with L-lysine at 2.65A resolution
  3qfe		Crystal structures of a putative dihydrodipicolinate synthase family protein from Coccidioides immitis
  3qze		Crystal Structure of DapA (PA1010) at 1.6 A resolution
  3rk8		Crystal structure of the chloride inhibited dihydrodipicolinate synthase from Acinetobacter baumannii complexed with pyruvate at 1.8 A resolution
  3s5n		Crystal Structure of Human 4-hydroxy-2-oxoglutarate Aldolase
  3s5o		Crystal Structure of Human 4-hydroxy-2-oxoglutarate Aldolase Bound to Pyruvate
  3s8h		Structure of dihydrodipicolinate synthase complexed with 3-Hydroxypropanoic acid(HPA)at 2.70 A resolution
  3si9		Crystal structure of Dihydrodipicolinate Synthase from Bartonella Henselae
  3tak		Crystal structure of the complex of DHDPS from Acinetobacter baumannii with Pyruvate at 1.4 A resolution
  3tce		Crystal structure of the complex of Dihydrodipicolinate synthase from Acinetobacter baumannii with 5-Hydroxylysine at 2.6 A resolution
  3tdf		Crystal structure of the complex of Dihydrodipicolinate synthase from Acinetobacter baumannii with 2-Ketobutanoic acid at 1.99 A resolution
  3tuu		Structure of dihydrodipicolinate synthase from the common grapevine
  3u8g		Crystal structure of the complex of Dihydrodipicolinate synthase from Acinetobacter baumannii with Oxalic acid at 1.80 A resolution
  3uqn		Crystal structure of dihydrodipicolinate synthase from Acinetobacter baumannii complexed with Oxamic acid at 1.9 Angstrom resolution
  3vfl		Structure, Function, Stability and Knockout Phenotype of Dihydrodipicolinate Synthase from Streptococcus pneumoniae
  4ah7		Structure of Wild Type Stapylococcus aureus N-acetylneuraminic acid lyase in complex with pyruvate
  4aho		Crystal Structure of N-acetylneuraminic acid lyase from Staphylococcus aureus with the chemical modification thia-lysine at position 165
  4ahp		Crystal Structure of Wild Type N-acetylneuraminic acid lyase from Staphylococcus aureus
  4ahq		Crystal Structure of N-acetylneuraminic acid lyase mutant K165C from Staphylococcus aureus
  4ama		Crystal Structure of N-acetylneuraminic acid lyase from Staphylococcus aureus with the chemical modification thia-lysine at position 165 in complex with pyruvate
  4bwl		Structure of the Y137A mutant of E. coli N-acetylneuraminic acid lyase in complex with pyruvate, N-acetyl-D-mannosamine and N- acetylneuraminic acid
  4dpp		The structure of dihydrodipicolinate synthase 2 from Arabidopsis thaliana
  4dpq		The structure of dihydrodipicolinate synthase 2 from Arabidopsis thaliana in complex with (S)-lysine
  4dxv		Crystal structure of Dihydrodipicolinate synthase from Acinetobacter baumannii complexed with Mg and Cl ions at 1.80 A resolution
  4eou		Crystal structure of E. coli dihydrodipicolinate synthase with pyruvate and succinic semi-aldehyde bound in active site
  4fha		Structure of Dihydrodipicolinate Synthase from Streptococcus pneumoniae,bound to pyruvate and lysine
  4hnn		Dihydrodipicolinate Synthase from the common grapevine with pyruvate and lysine
  4i7u		Dihydrodipicolinate Synthase of Agrobacterium tumefaciens
  4i7v		Agrobacterium tumefaciens DHDPS with pyruvate
  4i7w		Agrobacterium tumefaciens DHDPS with lysine and pyruvate
  4icn		Dihydrodipicolinate synthase from shewanella benthica
  4imc		Crystal Structure of Pasteurella multocida N-Acetyl-D-Neuraminic acid lyase
  4imd		Crystal Structure of Pasteurella multocida N-Acetyl-D-Neuraminic acid lyase trapped with pyruvate covalently bound through a Schiff base to Lys164
  4ime		Crystal Structure of Pasteurella multocida N-Acetyl-D-Neuraminic acid lyase K164A Mutant
  4imf		Crystal Structure of Pasteurella multocida N-Acetyl-D-Neuraminic acid lyase K164 mutant complexed with N-Acetylneuraminic acid
  4img		Crystal Structure of Pasteurella multocida N-Acetyl-D-Neuraminic acid lyase K164 mutant complexed with N-Glycolylneuraminic acid
  4ly8		4LY8
  4m19		4M19
  4mlj		4MLJ
  4mlr		4MLR
  4mpq		Crystal structure of1-pyrroline-4-hydroxy-2-carboxylate deaminase from Brucella melitensis ATCC 23457
  4n4p		Crystal Structure of N-acetylneuraminate lyase from Mycoplasma synoviae, crystal form I
  4n4q		Crystal Structure of N-acetylneuraminate lyase from Mycoplasma synoviae, crystal form II
  4nq1		Legionella pneumophila dihydrodipicolinate synthase with first substrate pyruvate bound in the active site
  4o0k		Crystal structure of 1-pyrroline-4-hydroxy-2-carboxylate deaminase from Brucella melitensis with covalently bound substrate
  4oe7		4OE7
  4onv		4ONV
  4pfm		4PFM
  4ptn		4PTN
  4r53		4R53
  4u4m		4U4M
  4ur7		4UR7
  4ur8		4UR8
  4uui		4UUI
  4uxd		4UXD
  4woq		4WOQ
  4woz		4WOZ
  4xky		4XKY
  5a8g		5A8G
  5afd		5AFD
  5c54		5C54
  5c55		5C55
  5czj		5CZJ
  5f1u		5F1U
  5f1v		5F1V
  5hwj		5HWJ
  5hwm		5HWM
  5hwn		5HWN
  5j5d		5J5D
  5ktl		5KTL
  5t26		5T26

• Links (links to other resources describing this domain)

• INTERPRO	IPR002220
  PFAM	DHDPS

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