DB code: D00007

CATH domain	3.40.50.720 : Rossmann fold	Catalytic domain
CATH domain	1.10.1040.10 : N-(1-d-carboxylethyl)-l-norvaline Dehydrogenase; domain 2
E.C.	1.1.1.35
CSA	2hdh
M-CSA	2hdh
MACiE

CATH domain	Related DB codes (homologues)
1.10.1040.10 : N-(1-d-carboxylethyl)-l-norvaline Dehydrogenase; domain 2	D00012 D00603 T00002 T00227
3.40.50.720 : Rossmann fold	S00543 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

CATH domain

Related DB codes (homologues)

1.10.1040.10 : N-(1-d-carboxylethyl)-l-norvaline Dehydrogenase; domain 2

D00012 D00603 T00002 T00227

3.40.50.720 : Rossmann fold

S00543 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

Uniprot Enzyme Name
UniprotKB	Protein name	Synonyms	RefSeq	Pfam
Q16836	Hydroxyacyl-coenzyme A dehydrogenase, mitochondrial	HCDH EC 1.1.1.35 Short chain 3-hydroxyacyl-CoA dehydrogenase Medium and short chain L-3-hydroxyacyl-coenzyme A dehydrogenase	NP_001171634.2 (Protein) NM_001184705.2 (DNA/RNA sequence) NP_005318.3 (Protein) NM_005327.4 (DNA/RNA sequence)	PF00725 (3HCDH) PF02737 (3HCDH_N) [Graphical View]
P00348	Hydroxyacyl-coenzyme A dehydrogenase, mitochondrial	HCDH EC 1.1.1.35 Short chain 3-hydroxyacyl-CoA dehydrogenase Medium and short chain L-3-hydroxyacyl-coenzyme A dehydrogenase	NP_999496.1 (Protein) NM_214331.1 (DNA/RNA sequence)	PF00725 (3HCDH) PF02737 (3HCDH_N) [Graphical View]

KEGG enzyme name
3-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

KEGG enzyme name

3-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

UniprotKB: Accession Number	Entry name	Activity	Subunit	Subcellular location	Cofactor
Q16836	HCDH_HUMAN	(S)-3-hydroxyacyl-CoA + NAD(+) = 3-oxoacyl-CoA + NADH.	Homodimer.	Mitochondrion matrix.
P00348	HCDH_PIG	(S)-3-hydroxyacyl-CoA + NAD(+) = 3-oxoacyl-CoA + NADH.	Homodimer.	Mitochondrion matrix.

KEGG Pathways
Map code	Pathways	E.C.
MAP00062	Fatty acid elongation in mitochondria
MAP00071	Fatty acid metabolism
MAP00280	Valine, leucine and isoleucine degradation
MAP00281	Geraniol degradation
MAP00310	Lysine degradation
MAP00380	Tryptophan metabolism
MAP00592	alpha-Linolenic acid metabolism
MAP00632	Benzoate degradation via CoA ligation
MAP00650	Butanoate metabolism
MAP00930	Caprolactam degradation

Compound table
	Substrates			Products				Intermediates
KEGG-id	C00003	C00640	C04405	C00004	C00264	C03344	C00080
E.C.
Compound	NAD+	(3S)-3-Hydroxyacyl-CoA	(2S,3S)-3-Hydroxy-2-methylbutanoyl-CoA	NADH	3-Oxoacyl-CoA	2-Methylacetoacetyl-CoA	H+
Type	amide group,amine group,nucleotide	amine group,carbohydrate,nucleotide ,peptide/protein,sulfide group	amine group,carbohydrate,nucleotide ,peptide/protein,sulfide group	amide group,amine group,nucleotide	amine group,carbohydrate,nucleotide ,peptide/protein,phosphate group/phosphate ion,sulfide group	amine group,carbohydrate,nucleotide ,peptide/protein,sulfide group	others
ChEBI	15846 15846		15449 15449	16908 16908		15476 15476	15378 15378
PubChem	5893 5893		11966220 440326 11966220 440326	439153 439153		193425 439985 193425 439985	1038 1038

1f0yA01	Bound:NAD	Unbound	Unbound	Unbound	Bound:CAA	Unbound
1f0yB01	Bound:NAD	Unbound	Unbound	Unbound	Bound:CAA	Unbound
1f12A01	Unbound	Bound:3HC	Unbound	Unbound	Unbound	Unbound
1f12B01	Unbound	Unbound	Unbound	Unbound	Unbound	Unbound
1f14A01	Unbound	Unbound	Unbound	Unbound	Unbound	Unbound
1f14B01	Unbound	Unbound	Unbound	Unbound	Unbound	Unbound
1f17A01	Unbound	Unbound	Unbound	Bound:NAI	Unbound	Unbound
1f17B01	Unbound	Unbound	Unbound	Bound:NAI	Unbound	Unbound
1il0A01	Bound:NAD	Unbound	Unbound	Unbound	Bound:CAA	Unbound
1il0B01	Bound:NAD	Unbound	Unbound	Unbound	Bound:CAA	Unbound
1lsjA01	Bound:NAD	Unbound	Unbound	Unbound	Unbound	Unbound
1lsjB01	Bound:NAD	Unbound	Unbound	Unbound	Unbound	Unbound
2hdhA01	Bound:NAD	Unbound	Unbound	Unbound	Unbound	Unbound
2hdhB01	Bound:NAD	Unbound	Unbound	Unbound	Unbound	Unbound
3hadA01	Bound:NAD	Unbound	Unbound	Unbound	Unbound	Unbound
3hadB01	Bound:NAD	Unbound	Unbound	Unbound	Unbound	Unbound
3hdhA01	Bound:NAD	Unbound	Unbound	Unbound	Unbound	Unbound
3hdhB01	Bound:NAD	Unbound	Unbound	Unbound	Unbound	Unbound
3hdhC01	Bound:NAD	Unbound	Unbound	Unbound	Unbound	Unbound
1f0yA02	Unbound	Unbound	Unbound	Unbound	Unbound	Unbound
1f0yB02	Unbound	Unbound	Unbound	Unbound	Unbound	Unbound
1f12A02	Unbound	Unbound	Unbound	Unbound	Unbound	Unbound
1f12B02	Unbound	Unbound	Unbound	Unbound	Unbound	Unbound
1f14A02	Unbound	Unbound	Unbound	Unbound	Unbound	Unbound
1f14B02	Unbound	Unbound	Unbound	Unbound	Unbound	Unbound
1f17A02	Unbound	Unbound	Unbound	Unbound	Unbound	Unbound
1f17B02	Unbound	Unbound	Unbound	Unbound	Unbound	Unbound
1il0A02	Unbound	Unbound	Unbound	Unbound	Unbound	Unbound
1il0B02	Unbound	Unbound	Unbound	Unbound	Unbound	Unbound
1lsjA02	Unbound	Unbound	Unbound	Unbound	Unbound	Unbound
1lsjB02	Unbound	Unbound	Unbound	Unbound	Unbound	Unbound
2hdhA02	Unbound	Unbound	Unbound	Unbound	Unbound	Unbound
2hdhB02	Unbound	Unbound	Unbound	Unbound	Unbound	Unbound
3hadA02	Unbound	Unbound	Unbound	Unbound	Unbound	Unbound
3hadB02	Unbound	Unbound	Unbound	Unbound	Unbound	Unbound
3hdhA02	Unbound	Unbound	Unbound	Unbound	Unbound	Unbound
3hdhB02	Unbound	Unbound	Unbound	Unbound	Unbound	Unbound
3hdhC02	Unbound	Unbound	Unbound	Unbound	Unbound	Unbound

Reference for Active-site residues
resource	references	E.C.
PDB;2hdh, 3had & Swiss-prot;Q16836, P00348 & literature [11], [18]

Active-site residues
PDB	Catalytic residues	Cofactor-binding residues	Modified residues	Main-chain involved in catalysis	Comment

1f0yA01	HIS 158;GLU 170
1f0yB01	HIS 158;GLU 170
1f12A01	HIS 158;GLU 170				mutant F80C
1f12B01	HIS 158;GLU 170				mutant F80C
1f14A01	HIS 158;GLU 170				mutant F80C
1f14B01	HIS 158;GLU 170				mutant F80C
1f17A01	HIS 158;GLU 170				mutant F80C
1f17B01	HIS 158;GLU 170				mutant F80C
1il0A01	HIS 158				mutant E170Q
1il0B01	HIS 158				mutant E170Q
1lsjA01	HIS 158;GLU 170				mutant E111Q
1lsjB01	HIS 158;GLU 170				mutant E111Q
2hdhA01	HIS 158;GLU 170				(3 selenomethionine)
2hdhB01	HIS 158;GLU 170				(3 selenomethionine)
3hadA01	HIS 158;GLU 170
3hadB01	HIS 158;GLU 170
3hdhA01	HIS 158;GLU 170
3hdhB01	HIS 158;GLU 170
3hdhC01	HIS 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
References	Sections	No. 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]
Resource
Comments
Medline ID
PubMed ID	7150615
Journal	Biochim Biophys Acta
Year	1982
Volume	713
Pages	270-9
Authors	El-Fakhri M, Middleton B
Title	The existence of an inner-membrane-bound, long acyl-chain-specific 3-hydroxyacyl-CoA dehydrogenase in mammalian mitochondria.
Related PDB
Related UniProtKB
[2]
Resource
Comments	X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS).
Medline ID
PubMed ID	3479790
Journal	Proc Natl Acad Sci U S A
Year	1987
Volume	84
Pages	8262-6
Authors	Birktoft JJ, Holden HM, Hamlin R, Xuong NH, Banaszak LJ
Title	Structure of L-3-hydroxyacyl-coenzyme A dehydrogenase: preliminary chain tracing at 2.8-A resolution.
Related PDB	3had 3hdh
Related UniProtKB	P00348
[3]
Resource
Comments
Medline ID
PubMed ID	1848777
Journal	Biochemistry
Year	1991
Volume	30
Pages	2782-90
Authors	Hartmann D, Philipp R, Schmadel K, Birktoft JJ, Banaszak LJ, Trommer WE
Title	Spatial arrangement of coenzyme and substrates bound to L-3-hydroxyacyl-CoA dehydrogenase as studied by spin-labeled analogues of NAD+ and CoA.
Related PDB
Related UniProtKB
[4]
Resource
Comments
Medline ID
PubMed ID	7756275
Journal	Biochemistry
Year	1995
Volume	34
Pages	6441-7
Authors	Yang SY, He XY, Schulz H
Title	Glutamate 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.
Related PDB
Related UniProtKB
[5]
Resource
Comments
Medline ID
PubMed ID	8687463
Journal	Biochem Biophys Res Commun
Year	1996
Volume	223
Pages	718-23
Authors	Vredendaal PJ, van den Berg IE, Malingre HE, Stroobants AK, Olde Weghuis DE, Berger R
Title	Human short-chain L-3-hydroxyacyl-CoA dehydrogenase: cloning and characterization of the coding sequence.
Related PDB
Related UniProtKB
[6]
Resource
Comments
Medline ID
PubMed ID	8755745
Journal	Biochemistry
Year	1996
Volume	35
Pages	9625-30
Authors	He XY, Yang SY
Title	Histidine-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.
Related PDB
Related UniProtKB
[7]
Resource
Comments
Medline ID
PubMed ID	9396725
Journal	Biochem J
Year	1997
Volume	328
Pages	815-20
Authors	Ishikawa M, Mikami Y, Usukura J, Iwasaki H, Shinagawa H, Morikawa K
Title	Reconstitution, morphology and crystallization of a fatty acid beta-oxidation multienzyme complex from Pseudomonas fragi.
Related PDB
Related UniProtKB
[8]
Resource
Comments
Medline ID
PubMed ID	8993342
Journal	Biochemistry
Year	1997
Volume	36
Pages	261-8
Authors	He XY, Deng H, Yang SY
Title	Importance 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.
Related PDB
Related UniProtKB
[9]
Resource
Comments
Medline ID
PubMed ID	9593854
Journal	Biochim Biophys Acta
Year	1998
Volume	1392
Pages	119-26
Authors	He XY, Yang SY
Title	Molecular cloning, expression in Escherichia coli, and characterization of a novel L-3-hydroxyacyl coenzyme A dehydrogenase from pig liver.
Related PDB
Related UniProtKB
[10]
Resource
Comments
Medline ID
PubMed ID	9716664
Journal	Mamm Genome
Year	1998
Volume	9
Pages	763-8
Authors	Vredendaal PJ, van den Berg IE, Stroobants AK, van der A DL, Malingre HE, Berger R
Title	Structural organization of the human short-chain L-3-hydroxyacyl-CoA dehydrogenase gene.
Related PDB
Related UniProtKB
[11]
Resource
Comments	X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 13-314.
Medline ID
PubMed ID	10231530
Journal	Biochemistry
Year	1999
Volume	38
Pages	5786-98
Authors	Barycki JJ, O'Brien LK, Bratt JM, Zhang R, Sanishvili R, Strauss AW, Banaszak LJ
Title	Biochemical characterization and crystal structure determination of human heart short chain L-3-hydroxyacyl-CoA dehydrogenase provide insights into catalytic mechanism.
Related PDB	2hdh
Related UniProtKB	Q16836
[12]
Resource
Comments
Medline ID
PubMed ID	10064895
Journal	Biochim Biophys Acta
Year	1999
Volume	1437
Pages	119-23
Authors	He XY, Zhang G, Blecha F, Yang SY
Title	Identity of heart and liver L-3-hydroxyacyl coenzyme A dehydrogenase.
Related PDB
Related UniProtKB
[13]
Resource
Comments
Medline ID
PubMed ID	10329704
Journal	J Biol Chem
Year	1999
Volume	274
Pages	15014-9
Authors	He XY, Merz G, Mehta P, Schulz H, Yang SY
Title	Human brain short chain L-3-hydroxyacyl coenzyme A dehydrogenase is a single-domain multifunctional enzyme. Characterization of a novel 17beta-hydroxysteroid dehydrogenase.
Related PDB
Related UniProtKB
[14]
Resource
Comments	X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS).
Medline ID
PubMed ID	10548046
Journal	Protein Sci
Year	1999
Volume	8
Pages	2010-8
Authors	Barycki JJ, O'Brien LK, Birktoft JJ, Strauss AW, Banaszak LJ
Title	Pig heart short chain L-3-hydroxyacyl-CoA dehydrogenase revisited: sequence analysis and crystal structure determination.
Related PDB	3hdh
Related UniProtKB	P00348
[15]
Resource
Comments
Medline ID
PubMed ID	10600649
Journal	Biochem J
Year	2000
Volume	345
Pages	139-43
Authors	He XY, Yang YZ, Schulz H, Yang SY
Title	Intrinsic alcohol dehydrogenase and hydroxysteroid dehydrogenase activities of human mitochondrial short-chain L-3-hydroxyacyl-CoA dehydrogenase.
Related PDB
Related UniProtKB
[16]
Resource
Comments
Medline ID
PubMed ID	10760475
Journal	Biochim Biophys Acta
Year	2000
Volume	1484
Pages	267-77
Authors	He XY, Merz G, Yang YZ, Pullakart R, Mehta P, Schulz H, Yang SY
Title	Function of human brain short chain L-3-hydroxyacyl coenzyme A dehydrogenase in androgen metabolism.
Related PDB
Related UniProtKB
[17]
Resource
Comments	X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 13-314.
Medline ID
PubMed ID	10840044
Journal	J Biol Chem
Year	2000
Volume	275
Pages	27186-96
Authors	Barycki JJ, O'Brien LK, Strauss AW, Banaszak LJ
Title	Sequestration of the active site by interdomain shifting. Crystallographic and spectroscopic evidence for distinct conformations of L-3-hydroxyacyl-CoA dehydrogenase.
Related PDB	1f0y 1f12 1f14 1f17
Related UniProtKB	Q16836
[18]
Resource
Comments	X-ray crystallography
Medline ID
PubMed ID	11451959
Journal	J Biol Chem
Year	2001
Volume	276
Pages	36718-26
Authors	Barycki JJ, O'Brien LK, Strauss AW, Banaszak LJ
Title	Glutamate 170 of human l-3-hydroxyacyl-CoA dehydrogenase is required for proper orientation of the catalytic histidine and structural integrity of the enzyme.
Related PDB	1il0
Related UniProtKB

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).

Created	Updated
2004-06-17	2009-02-26