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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Semialdhyde_dh Semialdehyde dehydrogenase, NAD binding domain

SMART accession number:	SM00859
Description:	The semialdehyde dehydrogenase family is found in N-acetyl-glutamine semialdehyde dehydrogenase (AgrC), which is involved in arginine biosynthesis, and aspartate-semialdehyde dehydrogenase, an enzyme involved in the biosynthesis of various amino acids from aspartate. This family is also found in yeast and fungal Arg5,6 protein, which is cleaved into the enzymes N-acety-gamma-glutamyl-phosphate reductase and acetylglutamate kinase. These are also involved in arginine biosynthesis. All proteins in this entry contain a NAD binding region of semialdehyde dehydrogenase.
Interpro abstract (IPR000534):	The semialdehyde dehydrogenase family is found in N-acetyl-glutamine semialdehyde dehydrogenase (AgrC), which is involved in arginine biosynthesis, and aspartate-semialdehyde dehydrogenase [ (PUBMED:10369777) ], an enzyme involved in the biosynthesis of various amino acids from aspartate. This family is also found in yeast and fungal Arg5,6 protein, which is cleaved into the enzymes N-acety-gamma-glutamyl-phosphate reductase and acetylglutamate kinase. These are also involved in arginine biosynthesis. All proteins in this entry contain a NAD binding region of semialdehyde dehydrogenase.
GO process:	oxidation-reduction process (GO:0055114)
GO function:	NAD binding (GO:0051287), oxidoreductase activity, acting on the aldehyde or oxo group of donors, NAD or NADP as acceptor (GO:0016620)
Family alignment:	View or CHROMA formatHMM/Web logoCLUSTALW formatMSF formatFASTA formatPIR format

There are 47211 Semialdhyde_dh domains in 47211 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 Semialdhyde_dh domain.

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

  Click on the protein counts, or double click on taxonomic names to display all proteins containing Semialdhyde_dh 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.

  • Hadfield A, Kryger G, Ouyang J, Petsko GA, Ringe D, Viola R
  • Structure of aspartate-beta-semialdehyde dehydrogenase from Escherichiacoli, a key enzyme in the aspartate family of amino acid biosynthesis.
  • J Mol Biol. 1999; 289: 991-1002
  • Display abstract

  • Aspartate beta-semialdehyde dehydrogenase (ASADH) lies at the first branchpoint in an essential aspartic biosynthetic pathway found in bacteria,fungi and the higher plants. Mutations in the asd gene encoding for ASADHthat produce an inactive enzyme are lethal, which suggests that ASADH maybe an effective target for antibacterial, herbicidal and fungicidalagents.We have solved the crystal structure of the Escherichia coli enzymeto 2.5 A resolution using single isomorphous replacement and 3-foldnon-crystallographic symmetry. Each monomer has an N-terminalnucleotide-binding domain and a dimerisation domain. The presence of anessential cysteine locates the active site in a cleft between the twodomains. The functional dimer has the appearance of a butterfly, with theNADP-binding domains forming the wings and the dimerisation domain formingthe body.A histidine residue is identified as a likely acid/base catalystin the enzymic reaction. Other amino acids implicated in the enzymicactivity by mutagenesis are found in the active site region and define thesubstrate binding pocket.

• Structure (3D structures containing this domain)

• 3D Structures of Semialdhyde_dh domains in PDB

  PDB code	Main view	Title
  1brm		ASPARTATE BETA-SEMIALDEHYDE DEHYDROGENASE FROM ESCHERICHIA COLI
  1gl3		ASPARTATE BETA-SEMIALDEHYDE DEHYDROGENASE IN COMPLEX WITH NADP AND SUBSTRATE ANALOGUE S-METHYL CYSTEINE SULFOXIDE
  1mb4		Crystal structure of aspartate semialdehyde dehydrogenase from vibrio cholerae with NADP and S-methyl-l-cysteine sulfoxide
  1mc4		Crystal Structure of Aspartate-Semialdehyde dehydrogenase from Vibrio Cholerae El Tor
  1nvm		Crystal structure of a bifunctional aldolase-dehydrogenase : sequestering a reactive and volatile intermediate
  1nwc		Crystal Structure of Aspartate-Semialdehyde Dehydrogenase from Haemophilus influenzae
  1nwh		Crystal Structure of Aspartate Semialdehyde Dehydrogenase from Haemophilus influenzae as a Tetrahedral Hemithioacetal Reaction Intermediate at 2.0 A
  1nx6		Crystal Structure of Aspartate Semialdehyde Dehydrogenase from Haemophilus influenzae as a Tetrahedral Hemithiocetal Reaction intermediate with Phosphate at 2.15 A
  1oza		Crystal Structure of the R103L Mutant of Aspartate Semialdehyde Dehydrogenase from Haemophilus influenzae
  1pqp		Crystal Structure of the C136S Mutant of Aspartate Semialdehyde Dehydrogenase from Haemophilus influenzae Bound with Aspartate Semialdehyde and Phosphate
  1pqu		Crystal Structure of the H277N Mutant of Aspartate Semialdehyde Dehydrogenase from Haemophilus influenzae Bound with NADP, S-methyl cysteine sulfoxide and cacodylate
  1pr3		Crystal Structure of the R103K Mutant of Aspartate Semialdehyde dehydrogenase from Haemophilus influenzae
  1ps8		Crystal Structure of the R270K Mutant of Aspartate Semialdehyde dehydrogenase from Haemophilus influenzae
  1pu2		Crystal Structure of the K246R Mutant of Aspartate Semialdehyde Dehydrogenase from Haemophilus influenzae
  1q2x		Crystal Structure of the E243D Mutant of Aspartate Semialdehyde Dehydrogenase from Haemophilus influenzae bound with substrate aspartate semialdehyde
  1t4b		1.6 Angstrom structure of Esherichia coli aspartate-semialdehyde dehydrogenase.
  1t4d		Crystal structure of Escherichia coli aspartate beta-semialdehyde dehydrogenase (EcASADH), at 1.95 Angstrom resolution
  1ta4		Crystal Structure Of Aspartate-Semialdehyde Dehydrogenase From Haemophilus Influenzae with a Bound Arsenate
  1tb4		Crystal Structure of Aspartate-Semialdehyde Dehydrogenase From Haemophilus influenzae with a Bound Periodate
  1vkn		Crystal structure of N-acetyl-gamma-glutamyl-phosphate reductase (TM1782) from Thermotoga maritima at 1.80 A resolution
  1xyg		X-RAY STRUCTURE OF GENE PRODUCT FROM ARABIDOPSIS THALIANA AT2G19940
  1ys4		Structure of Aspartate-Semialdehyde Dehydrogenase from Methanococcus jannaschii
  2cvo		Crystal structure of putative N-acetyl-gamma-glutamyl-phosphate reductase (AK071544) from rice (Oryza sativa)
  2ep5		Structural study of Project ID ST1242 from Sulfolobus tokodaii strain7
  2g17		The structure of N-acetyl-gamma-glutamyl-phosphate reductase from Salmonella typhimurium.
  2gyy		Structure of aspartate semialdehyde dehydrogenase (ASADH) from Streptococcus pneumoniae
  2gz1		Structure of Aspartate Semialdehyde Dehydrogenase (ASADH) from Streptococcus pneumoniae complexed with NADP
  2gz2		Structure of Aspartate Semialdehyde Dehydrogenase (ASADH) from Streptococcus pneumoniae complexed with 2',5'-ADP
  2gz3		Structure of Aspartate Semialdehyde Dehydrogenase (ASADH) from Streptococcus pneumoniae complexed with NADP and aspartate-semialdehyde
  2hjs		The structure of a probable aspartate-semialdehyde dehydrogenase from Pseudomonas aeruginosa
  2i3a		Crystal structure of N-Acetyl-gamma-Glutamyl-Phosphate Reductase (Rv1652) from Mycobacterium tuberculosis
  2i3g		Crystal structure of N-Acetyl-gamma-Glutamyl-Phosphate Reductase (Rv1652) from Mycobacterium tuberculosis in complex with NADP+.
  2nqt		Crystal structure of N-Acetyl-gamma-Glutamyl-Phosphate Reductase (Rv1652) from Mycobacterium tuberculosis at 1.58 A resolution
  2ozp		Crystal structure of N-acetyl-gamma-glutamyl-phosphate reductase (TTHA1904) from Thermus thermophilus
  2q49		Ensemble refinement of the protein crystal structure of gene product from Arabidopsis thaliana At2g19940
  2qz9		crystal structure of aspartate semialdehyde dehydrogenase II from vibrio cholerae
  2r00		crystal structure of aspartate semialdehyde dehydrogenase II complexed with ASA from vibrio cholerae
  2yv3		Crystal Structure of Aspartate Semialdehyde Dehydrogenase from Thermus thermophilus HB8
  3dr3		Structure of IDP00107, a potential N-acetyl-gamma-glutamylphosphate reductase from Shigella flexneri
  3hsk		Crystal Structure of Aspartate Semialdehyde Dehydrogenase with NADP from Candida albicans
  3pwk		Crystal Structure of Aspartate beta-Semialdehide Dehydrogenase from Streptococcus pneumoniae with 2',5'-Adenosine diphosphate and D-2-aminoadipate
  3pws		Crystal Structure of Aspartate beta-Semialdehide Dehydrogenase from Streptococcus pneumoniae with 2',5'-Adenosine diphosphate and D-2-aminoadipate
  3pyl		Crystal structure of aspartate beta-semialdehide dehydrogenase from Streptococcus pneumoniae with D-2,3-diaminopropionate
  3pyx		Crystals Structure of Aspartate beta-Semialdehyde Dehydrogenase complex with NADP and 2-aminoterephthalate
  3pzb		Crystals Structure of Aspartate beta-Semialdehyde Dehydrogenase complex with NADP and D-2,3-Diaminopropionate
  3pzr		Crystals structure of aspartate beta-Semialdehyde dehydrogenase from Vibrio Cholerae with NADP and product of S-carbamoyl-L-cysteine
  3q0e		Crystals Structure of Aspartate beta-Semialdehyde Dehydrogenase from Vibrio Cholerae with product of S-allyl-L-cysteine sulfoxide
  3q11		Crystals Structure of Aspartate beta-Semialdehyde Dehydrogenase from Streptococcus pneumoniae with NADP and aspartyl beta-difluorophosphonate
  3q1l		Crystals Structure of Aspartate beta-Semialdehyde Dehydrogenase from Streptococcus pneumoniae with cysteamine bound covalently to Cys 128
  3tz6		Crystal structure of Aspartate semialdehyde dehydrogenase Complexed With inhibitor SMCS (CYS) And Phosphate From Mycobacterium tuberculosis H37Rv
  3uw3		Crystal Structure of an Aspartate-Semialdehyde Dehydrogenase from Burkholderia Thailandensis
  3vos		Crystal structure of Aspartate semialdehyde dehydrogenase Complexed With glycerol and sulfate From Mycobacterium tuberculosis H37Rv
  4dpk		Structure of malonyl-coenzyme A reductase from crenarchaeota
  4dpl		Structure of malonyl-coenzyme A reductase from crenarchaeota in complex with NadP
  4dpm		Structure of malonyl-coenzyme A reductase from crenarchaeota in complex with CoA
  4jn6		Crystal Structure of the Aldolase-Dehydrogenase Complex from Mycobacterium tuberculosis HRv37
  4lrs		Crystal and solution structures of the bifunctional enzyme (Aldolase/Aldehyde dehydrogenase) from Thermomonospora curvata, reveal a cofactor-binding domain motion during NAD+ and CoA accommodation whithin the shared cofactor-binding site
  4lrt		Crystal and solution structures of the bifunctional enzyme (Aldolase/Aldehyde dehydrogenase) from Thermomonospora curvata, reveal a cofactor-binding domain motion during NAD+ and CoA accommodation whithin the shared cofactor-binding site
  4r3n		4R3N
  4r3w		4R3W
  4r41		4R41
  4r4j		4R4J
  4r51		4R51
  4r54		4R54
  4r5h		4R5H
  4r5m		4R5M
  4woj		4WOJ
  4zhs		4ZHS
  4zic		4ZIC
  5bnt		5BNT
  5cef		5CEF
  5ein		5EIN
  5eio		5EIO

• Links (links to other resources describing this domain)

• PFAM	Semialdhyde_dh
  INTERPRO	IPR000534

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