EzCatDB: D00007

DB codeD00007
CATH domainDomain 13.40.50.720Catalytic domain
Domain 21.10.1040.10
E.C.1.1.1.35
CSA2hdh

CATH domainRelated DB codes (homologues)
1.10.1040.10D00012,D00603,T00002,T00227
3.40.50.720S00543,S00551,S00552,S00553,S00602,S00604,S00605,S00608,S00610,S00625,S00319,S00328,S00329,S00330,S00331,S00332,D00456,D00457,D00458,S00324,S00320,S00325,S00326,S00327,D00459,S00335,S00336,S00334,T00219,S00339,D00513,D00001,D00002,D00003,D00005,D00008,D00010,D00012,D00017,D00018,D00023,D00027,D00028,D00031,D00032,D00033,D00034,D00035,D00037,D00048,D00071,D00476,D00481,D00482,D00490,D00492,D00494,D00545,D00601,D00603,D00604,D00605,D00615,D00845,D00857,D00858,M00161,M00171,M00210,T00002,T00010,T00011,T00015,T00227,T00247,T00408,T00414,D00827,D00262,D00274,D00275,M00035,T00109

Enzyme Name
Swiss-protKEGG

Q16836P00348
Protein nameHydroxyacyl-coenzyme A dehydrogenase, mitochondrialHydroxyacyl-coenzyme A dehydrogenase, mitochondrial3-hydroxyacyl-CoA dehydrogenase
beta-hydroxyacyl dehydrogenase
beta-keto-reductase
3-keto reductase
3-hydroxyacyl coenzyme A dehydrogenase
beta-hydroxyacyl-coenzyme A synthetase
beta-hydroxyacylcoenzyme A dehydrogenase
beta-hydroxybutyrylcoenzyme A dehydrogenase
3-hydroxyacetyl-coenzyme A dehydrogenase
L-3-hydroxyacyl coenzyme A dehydrogenase
L-3-hydroxyacyl CoA dehydrogenase
beta-hydroxyacyl CoA dehydrogenase
3beta-hydroxyacyl coenzyme A dehydrogenase
3-hydroxybutyryl-CoA dehydrogenase
beta-ketoacyl-CoA reductase
beta-hydroxy acid dehydrogenase
3-L-hydroxyacyl-CoA dehydrogenase
3-hydroxyisobutyryl-CoA dehydrogenase
1-specific DPN-linked beta-hydroxybutyric dehydrogenase
SynonymsHCDH
EC 1.1.1.35
Short chain 3-hydroxyacyl-CoA dehydrogenase
Medium and short chain L-3-hydroxyacyl-coenzyme A dehydrogenase
HCDH
EC 1.1.1.35
Short chain 3-hydroxyacyl-CoA dehydrogenase
Medium and short chain L-3-hydroxyacyl-coenzyme A dehydrogenase

KEGG pathways
MAP codePathways
MAP00062Fatty acid elongation in mitochondria
MAP00071Fatty acid metabolism
MAP00280Valine, leucine and isoleucine degradation
MAP00281Geraniol degradation
MAP00310Lysine degradation
MAP00380Tryptophan metabolism
MAP00592alpha-Linolenic acid metabolism
MAP00632Benzoate degradation via CoA ligation
MAP00650Butanoate metabolism
MAP00930Caprolactam degradation

Swiss-prot:Accession NumberQ16836P00348
Entry nameHCDH_HUMANHCDH_PIG
Activity(S)-3-hydroxyacyl-CoA + NAD(+) = 3-oxoacyl-CoA + NADH.(S)-3-hydroxyacyl-CoA + NAD(+) = 3-oxoacyl-CoA + NADH.
SubunitHomodimer.Homodimer.
Subcellular locationMitochondrion matrix.Mitochondrion matrix.
Cofactor



SubstratesProducts
KEGG-idC00003C00640C04405C00004C00264C03344C00080
CompoundNAD+(3S)-3-Hydroxyacyl-CoA(2S,3S)-3-Hydroxy-2-methylbutanoyl-CoANADH3-Oxoacyl-CoA2-Methylacetoacetyl-CoAH+
Typeamide group,amine group,nucleotideamine group,carbohydrate,nucleotide,peptide/protein,sulfide groupamine group,carbohydrate,nucleotide,peptide/protein,sulfide groupamide group,amine group,nucleotideamine group,carbohydrate,nucleotide,peptide/protein,phosphate group/phosphate ion,sulfide groupamine group,carbohydrate,nucleotide,peptide/protein,sulfide groupothers
1f0yA01Bound:NADUnboundUnboundUnboundBound:CAAUnbound
1f0yB01Bound:NADUnboundUnboundUnboundBound:CAAUnbound
1f12A01UnboundBound:3HCUnboundUnboundUnboundUnbound
1f12B01UnboundUnboundUnboundUnboundUnboundUnbound
1f14A01UnboundUnboundUnboundUnboundUnboundUnbound
1f14B01UnboundUnboundUnboundUnboundUnboundUnbound
1f17A01UnboundUnboundUnboundBound:NAIUnboundUnbound
1f17B01UnboundUnboundUnboundBound:NAIUnboundUnbound
1il0A01Bound:NADUnboundUnboundUnboundBound:CAAUnbound
1il0B01Bound:NADUnboundUnboundUnboundBound:CAAUnbound
1lsjA01Bound:NADUnboundUnboundUnboundUnboundUnbound
1lsjB01Bound:NADUnboundUnboundUnboundUnboundUnbound
2hdhA01Bound:NADUnboundUnboundUnboundUnboundUnbound
2hdhB01Bound:NADUnboundUnboundUnboundUnboundUnbound
3hadA01Bound:NADUnboundUnboundUnboundUnboundUnbound
3hadB01Bound:NADUnboundUnboundUnboundUnboundUnbound
3hdhA01Bound:NADUnboundUnboundUnboundUnboundUnbound
3hdhB01Bound:NADUnboundUnboundUnboundUnboundUnbound
3hdhC01Bound:NADUnboundUnboundUnboundUnboundUnbound
1f0yA02UnboundUnboundUnboundUnboundUnboundUnbound
1f0yB02UnboundUnboundUnboundUnboundUnboundUnbound
1f12A02UnboundUnboundUnboundUnboundUnboundUnbound
1f12B02UnboundUnboundUnboundUnboundUnboundUnbound
1f14A02UnboundUnboundUnboundUnboundUnboundUnbound
1f14B02UnboundUnboundUnboundUnboundUnboundUnbound
1f17A02UnboundUnboundUnboundUnboundUnboundUnbound
1f17B02UnboundUnboundUnboundUnboundUnboundUnbound
1il0A02UnboundUnboundUnboundUnboundUnboundUnbound
1il0B02UnboundUnboundUnboundUnboundUnboundUnbound
1lsjA02UnboundUnboundUnboundUnboundUnboundUnbound
1lsjB02UnboundUnboundUnboundUnboundUnboundUnbound
2hdhA02UnboundUnboundUnboundUnboundUnboundUnbound
2hdhB02UnboundUnboundUnboundUnboundUnboundUnbound
3hadA02UnboundUnboundUnboundUnboundUnboundUnbound
3hadB02UnboundUnboundUnboundUnboundUnboundUnbound
3hdhA02UnboundUnboundUnboundUnboundUnboundUnbound
3hdhB02UnboundUnboundUnboundUnboundUnboundUnbound
3hdhC02UnboundUnboundUnboundUnboundUnboundUnbound

Active-site residues
resource
PDB;2hdh, 3had & Swiss-prot;Q16836, P00348 & literature [11], [18]
pdbCatalytic residuescomment
1f0yA01HIS 158;GLU 170

1f0yB01HIS 158;GLU 170

1f12A01HIS 158;GLU 170
mutant F80C
1f12B01HIS 158;GLU 170
mutant F80C
1f14A01HIS 158;GLU 170
mutant F80C
1f14B01HIS 158;GLU 170
mutant F80C
1f17A01HIS 158;GLU 170
mutant F80C
1f17B01HIS 158;GLU 170
mutant F80C
1il0A01HIS 158        
mutant E170Q
1il0B01HIS 158        
mutant E170Q
1lsjA01HIS 158;GLU 170
mutant E111Q
1lsjB01HIS 158;GLU 170
mutant E111Q
2hdhA01HIS 158;GLU 170
(3 selenomethionine)
2hdhB01HIS 158;GLU 170
(3 selenomethionine)
3hadA01HIS 158;GLU 170

3hadB01HIS 158;GLU 170

3hdhA01HIS 158;GLU 170

3hdhB01HIS 158;GLU 170

3hdhC01HIS 158;GLU 170

1f0yA02

1f0yB02

1f12A02

1f12B02

1f14A02

1f14B02

1f17A02

1f17B02

1il0A02

1il0B02

1lsjA02

1lsjB02

2hdhA02
(4 selenomethionine)
2hdhB02
(4 selenomethionine)
3hadA02

3hadB02

3hdhA02

3hdhB02

3hdhC02


References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[4]p.6444-6445
[8]Fig.3, p.265-268
[11]Fig.7, p.5795-5797
[17]

[18]SCHEME 1

references
[1]
PubMed ID7150615
JournalBiochim Biophys Acta
Year1982
Volume713
Pages270-9
AuthorsEl-Fakhri M, Middleton B
TitleThe existence of an inner-membrane-bound, long acyl-chain-specific 3-hydroxyacyl-CoA dehydrogenase in mammalian mitochondria.
[2]
CommentsX-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS).
PubMed ID3479790
JournalProc Natl Acad Sci U S A
Year1987
Volume84
Pages8262-6
AuthorsBirktoft JJ, Holden HM, Hamlin R, Xuong NH, Banaszak LJ
TitleStructure of L-3-hydroxyacyl-coenzyme A dehydrogenase: preliminary chain tracing at 2.8-A resolution.
Related PDB3had,3hdh
Related Swiss-protP00348
[3]
PubMed ID1848777
JournalBiochemistry
Year1991
Volume30
Pages2782-90
AuthorsHartmann D, Philipp R, Schmadel K, Birktoft JJ, Banaszak LJ, Trommer WE
TitleSpatial arrangement of coenzyme and substrates bound to L-3-hydroxyacyl-CoA dehydrogenase as studied by spin-labeled analogues of NAD+ and CoA.
[4]
PubMed ID7756275
JournalBiochemistry
Year1995
Volume34
Pages6441-7
AuthorsYang SY, He XY, Schulz H
TitleGlutamate 139 of the large alpha-subunit is the catalytic base in the dehydration of both D- and L-3-hydroxyacyl-coenzyme A but not in the isomerization of delta 3, delta 2-enoyl-coenzyme A catalyzed by the multienzyme complex of fatty acid oxidation from Escherichia coli.
[5]
PubMed ID8687463
JournalBiochem Biophys Res Commun
Year1996
Volume223
Pages718-23
AuthorsVredendaal PJ, van den Berg IE, Malingre HE, Stroobants AK, Olde Weghuis DE, Berger R
TitleHuman short-chain L-3-hydroxyacyl-CoA dehydrogenase: cloning and characterization of the coding sequence.
[6]
PubMed ID8755745
JournalBiochemistry
Year1996
Volume35
Pages9625-30
AuthorsHe XY, Yang SY
TitleHistidine-450 is the catalytic residue of L-3-hydroxyacyl coenzyme A dehydrogenase associated with the large alpha-subunit of the multienzyme complex of fatty acid oxidation from Escherichia coli.
[7]
PubMed ID9396725
JournalBiochem J
Year1997
Volume328
Pages815-20
AuthorsIshikawa M, Mikami Y, Usukura J, Iwasaki H, Shinagawa H, Morikawa K
TitleReconstitution, morphology and crystallization of a fatty acid beta-oxidation multienzyme complex from Pseudomonas fragi.
[8]
PubMed ID8993342
JournalBiochemistry
Year1997
Volume36
Pages261-8
AuthorsHe XY, Deng H, Yang SY
TitleImportance of the gamma-carboxyl group of glutamate-462 of the large alpha-subunit for the catalytic function and the stability of the multienzyme complex of fatty acid oxidation from Escherichia coli.
[9]
PubMed ID9593854
JournalBiochim Biophys Acta
Year1998
Volume1392
Pages119-26
AuthorsHe XY, Yang SY
TitleMolecular cloning, expression in Escherichia coli, and characterization of a novel L-3-hydroxyacyl coenzyme A dehydrogenase from pig liver.
[10]
PubMed ID9716664
JournalMamm Genome
Year1998
Volume9
Pages763-8
AuthorsVredendaal PJ, van den Berg IE, Stroobants AK, van der A DL, Malingre HE, Berger R
TitleStructural organization of the human short-chain L-3-hydroxyacyl-CoA dehydrogenase gene.
[11]
CommentsX-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 13-314.
PubMed ID10231530
JournalBiochemistry
Year1999
Volume38
Pages5786-98
AuthorsBarycki JJ, O'Brien LK, Bratt JM, Zhang R, Sanishvili R, Strauss AW, Banaszak LJ
TitleBiochemical characterization and crystal structure determination of human heart short chain L-3-hydroxyacyl-CoA dehydrogenase provide insights into catalytic mechanism.
Related PDB2hdh
Related Swiss-protQ16836
[12]
PubMed ID10064895
JournalBiochim Biophys Acta
Year1999
Volume1437
Pages119-23
AuthorsHe XY, Zhang G, Blecha F, Yang SY
TitleIdentity of heart and liver L-3-hydroxyacyl coenzyme A dehydrogenase.
[13]
PubMed ID10329704
JournalJ Biol Chem
Year1999
Volume274
Pages15014-9
AuthorsHe XY, Merz G, Mehta P, Schulz H, Yang SY
TitleHuman brain short chain L-3-hydroxyacyl coenzyme A dehydrogenase is a single-domain multifunctional enzyme. Characterization of a novel 17beta-hydroxysteroid dehydrogenase.
[14]
CommentsX-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS).
PubMed ID10548046
JournalProtein Sci
Year1999
Volume8
Pages2010-8
AuthorsBarycki JJ, O'Brien LK, Birktoft JJ, Strauss AW, Banaszak LJ
TitlePig heart short chain L-3-hydroxyacyl-CoA dehydrogenase revisited: sequence analysis and crystal structure determination.
Related PDB3hdh
Related Swiss-protP00348
[15]
PubMed ID10600649
JournalBiochem J
Year2000
Volume345
Pages139-43
AuthorsHe XY, Yang YZ, Schulz H, Yang SY
TitleIntrinsic alcohol dehydrogenase and hydroxysteroid dehydrogenase activities of human mitochondrial short-chain L-3-hydroxyacyl-CoA dehydrogenase.
[16]
PubMed ID10760475
JournalBiochim Biophys Acta
Year2000
Volume1484
Pages267-77
AuthorsHe XY, Merz G, Yang YZ, Pullakart R, Mehta P, Schulz H, Yang SY
TitleFunction of human brain short chain L-3-hydroxyacyl coenzyme A dehydrogenase in androgen metabolism.
[17]
CommentsX-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 13-314.
PubMed ID10840044
JournalJ Biol Chem
Year2000
Volume275
Pages27186-96
AuthorsBarycki JJ, O'Brien LK, Strauss AW, Banaszak LJ
TitleSequestration of the active site by interdomain shifting. Crystallographic and spectroscopic evidence for distinct conformations of L-3-hydroxyacyl-CoA dehydrogenase.
Related PDB1f0y,1f12,1f14,1f17
Related Swiss-protQ16836
[18]
CommentsX-ray crystallography
PubMed ID11451959
JournalJ Biol Chem
Year2001
Volume276
Pages36718-26
AuthorsBarycki JJ, O'Brien LK, Strauss AW, Banaszak LJ
TitleGlutamate 170 of human l-3-hydroxyacyl-CoA dehydrogenase is required for proper orientation of the catalytic histidine and structural integrity of the enzyme.
Related PDB1il0

comments
Hi158 acts as a general base, whereas Glu170 acts as a modulator for the base. Ser137 & Asn208 might be also catalytic (see [11]).
###
This enzyme also oxidizes S-3-hydroxyacyl-N-acylthioethanolamine and S-3-hydroxyacylhydrolipoate.
The enzymes (E.C. 1.1.1.211) acts on chain length C(8) or C(10).

createdupdated
2004-06-172009-02-26


Copyright: Nozomi Nagano, JST & CBRC-AIST
Funded by PRESTO/Japan Science and Technology Corporation (JST) (December 2001 - November 2004)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2006)
Funded by Grant-in-Aid for Scientific Research (B)/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2008)
Funded by BIRD/Japan Science and Technology Corporation (JST) (September 2005 - September 2010)
Funded by BIRD/Japan Science and Technology Corporation (JST) (October 2007 - September 2010)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2011 - March 2012)

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