D00003
type: Enzyme
cath: Rossmann fold
cath: Dihydrodipicolinate Reductase; domain 2
ec: https://purl.uniprot.org/enzyme/1.1.1.3
csa: 1ebf
uniprot: P31116
kegg enzyme: homoserine dehydrogenase
kegg enzyme: HSDH
kegg enzyme: HSD
kegg pathway: Glycine, serine and threonine metabolism
kegg pathway: Lysine biosynthesis
kegg substrate: L-Homoserine
kegg substrate: NAD+
kegg substrate: NADP+
kegg product: L-Aspartate 4-semialdehyde
kegg product: NADH
kegg product: NADPH
kegg product: H+
pdb: 1ebfA01
pdb: 1ebfB01
pdb: 1ebuA01
pdb: 1ebuB01
pdb: 1ebuC01
pdb: 1ebuD01
pdb: 1q7gA01
pdb: 1q7gB01
pdb: 1tveA01
pdb: 1tveB01
pdb: 1ebfA02
pdb: 1ebfB02
pdb: 1ebuA02
pdb: 1ebuB02
pdb: 1ebuC02
pdb: 1ebuD02
pdb: 1q7gA02
pdb: 1q7gB02
pdb: 1tveA02
pdb: 1tveB02
pdb bound state: Unbound
  compound: L-Homoserine
  pdb: 1ebfA01
pdb bound state: Unbound
  compound: L-Homoserine
  pdb: 1ebfB01
pdb bound state: Unbound
  compound: L-Homoserine
  pdb: 1ebuA01
pdb bound state: Unbound
  compound: L-Homoserine
  pdb: 1ebuB01
pdb bound state: Unbound
  compound: L-Homoserine
  pdb: 1ebuC01
pdb bound state: Unbound
  compound: L-Homoserine
  pdb: 1ebuD01
pdb bound state: Unbound
  compound: L-Homoserine
  pdb: 1q7gA01
pdb bound state: Unbound
  compound: L-Homoserine
  pdb: 1q7gB01
pdb bound state: Unbound
  compound: L-Homoserine
  pdb: 1tveA01
pdb bound state: Unbound
  compound: L-Homoserine
  pdb: 1tveB01
pdb bound state: Unbound
  compound: L-Homoserine
  pdb: 1ebfA02
pdb bound state: Unbound
  compound: L-Homoserine
  pdb: 1ebfB02
pdb bound state: Unbound
  compound: L-Homoserine
  pdb: 1ebuA02
pdb bound state: Unbound
  compound: L-Homoserine
  pdb: 1ebuB02
pdb bound state: Unbound
  compound: L-Homoserine
  pdb: 1ebuC02
pdb bound state: Unbound
  compound: L-Homoserine
  pdb: 1q7gA02
pdb bound state: Unbound
  compound: L-Homoserine
  pdb: 1q7gB02
pdb bound state: Unbound
  compound: L-Homoserine
  pdb: 1tveA02
pdb bound state: Unbound
  compound: L-Homoserine
  pdb: 1tveB02
pdb bound state: Unbound
  compound: NAD+
  pdb: 1ebfB01
pdb bound state: Unbound
  compound: NAD+
  pdb: 1ebuA01
pdb bound state: Unbound
  compound: NAD+
  pdb: 1ebuB01
pdb bound state: Unbound
  compound: NAD+
  pdb: 1ebuC01
pdb bound state: Analogue
  compound: NAD+
  pdb: 1ebuD01
  ligand het code: NDA
active site residues resources: Homoserine dehydrogenase from Saccharomyces cerevisiae: kinetic mechanism and stereochemistry of hydride transfer.
references: Studies on the catalytic and regulatory properties of homoserine dehydrogenase of Zea mays roots.
references: Effects of K+ on the catalytic and regulatory properties of homoserine dehydrogenase of Pseudomonas fluorescens.
references: The threonine-sensitive homoserine dehydrogenase and aspartokinase activities of Escherichia coli K12. The two catalytic activities are carried by two independent regions of the polypeptide chain.
references: The threonine-sensitive homoserine dehydrogenase and aspartokinase activities of Escherichia coli K 12. Intra and intersubunit interactions between the catalytic regions of the bifunctional enzyme.
references: Cobalt(III) affinity-labeled aspartokinase. Formation of substrate and inhibitor adducts.
references: Homoserine dehydrogenase of Rhodospirillum rubrum. Physical and chemical characterization.
references: Sequential folding of a bifunctional allosteric protein.
references: The interaction between Escherichia coli aspartokinase-homoserine dehydrogenase and 3-acetylpyridine-adenine dinucleotide phosphate (reduced), an analog of NADPH.
references: The kinetic mechanisms of the bifunctional enzyme aspartokinase-homoserine dehydrogenase I from Escherichia coli.
references: Role of serine 352 in the allosteric response of Serratia marcescens aspartokinase I-homoserine dehydrogenase I analyzed by using site-directed mutagenesis.
references: Crystallization and preliminary X-ray diffraction studies of homoserine dehydrogenase from Saccharomyces cerevisiae.
references: Crystal structures of homoserine dehydrogenase suggest a novel catalytic mechanism for oxidoreductases.
references: Homoserine dehydrogenase from Saccharomyces cerevisiae: kinetic mechanism and stereochemistry of hydride transfer.
references: Characterization of yeast homoserine dehydrogenase, an antifungal target: the invariant histidine 309 is important for enzyme integrity.
references: Production and characterization of bifunctional enzymes. Domain swapping to produce new bifunctional enzymes in the aspartate pathway.
references: Enzyme-assisted suicide: molecular basis for the antifungal activity of 5-hydroxy-4-oxonorvaline by potent inhibition of homoserine dehydrogenase.
references: New phenolic inhibitors of yeast homoserine dehydrogenase.

Rossmann fold
type: Cath
references: http://www.cathdb.info/version/latest/superfamily/3.40.50.720

Dihydrodipicolinate Reductase; domain 2
type: Cath
references: http://www.cathdb.info/version/latest/superfamily/3.30.360.10
catalytic domain: index.html

Glycine, serine and threonine metabolism
type: KeggPathway
references: KEGG:MAP00260

Lysine biosynthesis
type: KeggPathway
references: KEGG:MAP00300

L-Homoserine
type: KeggSubstrate
references: KEGG:C00263
compound type: amino acids
compound type: carbohydrate
references: CHEBI:15699
references: CHEBI:57476
references: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi

NAD+
type: KeggSubstrate
references: KEGG:C00003
compound type: amide group
compound type: amine group
compound type: nucleotide
references: CHEBI:15846
references: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi

NADP+
type: KeggSubstrate
references: KEGG:C00006
compound type: amide group
compound type: amine group
compound type: nucleotide
references: CHEBI:18009
references: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi

L-Aspartate 4-semialdehyde
type: KeggProduct
references: KEGG:C00441
compound type: amino acids
compound type: carbohydrate
references: CHEBI:18051
references: CHEBI:537519
references: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi

NADH
type: KeggProduct
references: KEGG:C00004
compound type: amide group
compound type: amine group
compound type: nucleotide
references: CHEBI:16908
references: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi

NADPH
type: KeggProduct
references: KEGG:C00005
compound type: amide group
compound type: amine group
compound type: nucleotide
references: CHEBI:16474
references: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi

H+
type: KeggProduct
references: KEGG:C00080
compound type: others
references: CHEBI:15378
references: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi

1ebfA02
type: Pdb
references: 1ebf
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1ebf
catalytic residue: ASP 219;LYS 223

1ebfB02
type: Pdb
references: 1ebf
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1ebf
catalytic residue: ASP 219;LYS 223

1ebuA02
type: Pdb
references: 1ebu
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1ebu
catalytic residue: ASP 219;LYS 223

1ebuB02
type: Pdb
references: 1ebu
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1ebu
catalytic residue: ASP 219;LYS 223

1ebuC02
type: Pdb
references: 1ebu
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1ebu
catalytic residue: ASP 219;LYS 223

1ebuD02
type: Pdb
references: 1ebu
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1ebu
catalytic residue: ASP 219;LYS 223

1q7gA02
type: Pdb
references: 1q7g
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1q7g
catalytic residue: ASP 219;LYS 223

1q7gB02
type: Pdb
references: 1q7g
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1q7g
catalytic residue: ASP 219;LYS 223

1tveA02
type: Pdb
references: 1tve
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1tve
catalytic residue: ASP 219;LYS 223

1tveB02
type: Pdb
references: 1tve
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1tve
catalytic residue: ASP 219;LYS 223

Studies on the catalytic and regulatory properties of homoserine dehydrogenase of Zea mays roots.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/4388077
journal: Biochim Biophys Acta
volume: 171
pages: 205-16
published year: 1969
authors:
  item: Bryan JK

Effects of K+ on the catalytic and regulatory properties of homoserine dehydrogenase of Pseudomonas fluorescens.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/4397398
journal: Biochim Biophys Acta
volume: 235
pages: 1-13
published year: 1971
authors:
  item: Bothwell MA
  item: Datta P

The threonine-sensitive homoserine dehydrogenase and aspartokinase activities of Escherichia coli K12. The two catalytic activities are carried by two independent regions of the polypeptide chain.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/4562990
journal: Eur J Biochem
volume: 28
pages: 520-7
published year: 1972
authors:
  item: Veron M
  item: Falcoz-Kelly F
  item: Cohen GN

The threonine-sensitive homoserine dehydrogenase and aspartokinase activities of Escherichia coli K 12. Intra and intersubunit interactions between the catalytic regions of the bifunctional enzyme.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/4149354
journal: Eur J Biochem
volume: 38
pages: 325-35
published year: 1973
authors:
  item: Veron M
  item: Saari JC
  item: Villar-Palasi C
  item: Cohen GN

Cobalt(III) affinity-labeled aspartokinase. Formation of substrate and inhibitor adducts.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/182215
journal: Biochemistry
volume: 15
pages: 3704-10
published year: 1976
authors:
  item: Wright JK
  item: Feldman J
  item: Takahashi M

Homoserine dehydrogenase of Rhodospirillum rubrum. Physical and chemical characterization.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/414912
journal: Eur J Biochem
volume: 82
pages: 453-61
published year: 1978
authors:
  item: Epstein CC
  item: Datta P

Sequential folding of a bifunctional allosteric protein.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/6774337
journal: Proc Natl Acad Sci U S A
volume: 77
pages: 3379-83
published year: 1980
authors:
  item: Garel JR
  item: Dautry-Varsat A

The interaction between Escherichia coli aspartokinase-homoserine dehydrogenase and 3-acetylpyridine-adenine dinucleotide phosphate (reduced), an analog of NADPH.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/6365907
journal: J Biol Chem
volume: 259
pages: 2252-6
published year: 1984
authors:
  item: Muller K
  item: Garel JR

The kinetic mechanisms of the bifunctional enzyme aspartokinase-homoserine dehydrogenase I from Escherichia coli.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/2241177
journal: Arch Biochem Biophys
volume: 283
pages: 96-101
published year: 1990
authors:
  item: Angeles TS
  item: Viola RE

Role of serine 352 in the allosteric response of Serratia marcescens aspartokinase I-homoserine dehydrogenase I analyzed by using site-directed mutagenesis.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/8432719
journal: J Bacteriol
volume: 175
pages: 959-65
published year: 1993
authors:
  item: Omori K
  item: Komatsubara S

Crystallization and preliminary X-ray diffraction studies of homoserine dehydrogenase from Saccharomyces cerevisiae.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/9761913
journal: Acta Crystallogr D Biol Crystallogr
volume: 54
pages: 413-5
published year: 1998
authors:
  item: DeLaBarre B
  item: Jacques SL
  item: Pratt CE
  item: Ruth DA
  item: Wright GD
  item: Berghuis AM

Crystal structures of homoserine dehydrogenase suggest a novel catalytic mechanism for oxidoreductases.
type: BibliographicResource
comment: X-ray crystallography
references: http://www.ncbi.nlm.nih.gov/pubmed/10700284
journal: Nat Struct Biol
volume: 7
pages: 238-44
published year: 2000
authors:
  item: DeLaBarre B
  item: Thompson PR
  item: Wright GD
  item: Berghuis AM
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl

Homoserine dehydrogenase from Saccharomyces cerevisiae: kinetic mechanism and stereochemistry of hydride transfer.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/11341915
journal: Biochim Biophys Acta
volume: 1544
pages: 42-54
published year: 2001
authors:
  item: Jacques SL
  item: Ejim LJ
  item: Wright GD

Characterization of yeast homoserine dehydrogenase, an antifungal target: the invariant histidine 309 is important for enzyme integrity.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/11341914
journal: Biochim Biophys Acta
volume: 1544
pages: 28-41
published year: 2001
authors:
  item: Jacques SL
  item: Nieman C
  item: Bareich D
  item: Broadhead G
  item: Kinach R
  item: Honek JF
  item: Wright GD

Production and characterization of bifunctional enzymes. Domain swapping to produce new bifunctional enzymes in the aspartate pathway.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/11888289
journal: Biochemistry
volume: 41
pages: 3720-5
published year: 2002
authors:
  item: James CL
  item: Viola RE

Enzyme-assisted suicide: molecular basis for the antifungal activity of 5-hydroxy-4-oxonorvaline by potent inhibition of homoserine dehydrogenase.
type: BibliographicResource
comment: X-ray crystallography
references: http://www.ncbi.nlm.nih.gov/pubmed/14583265
journal: Chem Biol
volume: 10
pages: 989-95
published year: 2003
authors:
  item: Jacques SL
  item: Mirza IA
  item: Ejim L
  item: Koteva K
  item: Hughes DW
  item: Green K
  item: Kinach R
  item: Honek JF
  item: Lai HK
  item: Berghuis AM
  item: Wright GD
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl

New phenolic inhibitors of yeast homoserine dehydrogenase.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/15210149
journal: Bioorg Med Chem
volume: 12
pages: 3825-30
published year: 2004
authors:
  item: Ejim L
  item: Mirza IA
  item: Capone C
  item: Nazi I
  item: Jenkins S
  item: Chee GL
  item: Berghuis AM
  item: Wright GD
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl

Analogue
compound: NAD+
pdb: 1q7gA01
ligand het code: NHO

ReferenceForCatalyticMechanism
reference index: 12
reference section: Fig.5a, p.242-243

ReferenceForCatalyticMechanism
reference index: 13
reference section: Scheme 1, Scheme 2, p.51-53