DB code: S00610

RLCP classification	9.1050.440000.8010 : Hydride transfer
RLCP classification	9.5010.536200.8010 : Hydride transfer
CATH domain	3.40.50.720 : Rossmann fold	Catalytic domain
E.C.	1.1.1.51
CSA
M-CSA
MACiE

CATH domain	Related DB codes (homologues)
3.40.50.720 : Rossmann fold	S00543 S00551 S00552 S00553 S00602 S00604 S00605 S00608 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 D00007 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)

3.40.50.720 : Rossmann fold

S00543 S00551 S00552 S00553 S00602 S00604 S00605 S00608 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 D00007 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	Pfam
P19871	3-beta-hydroxysteroid dehydrogenase	EC 1.1.1.51	PF00106 (adh_short) [Graphical View]

KEGG enzyme name
3(or 17)beta-Hydroxysteroid dehydrogenase beta-Hydroxy steroid dehydrogenase 17-Ketoeductase 17beta-Hydroxy steroid dehydrogenase 3beta-Hydroxysteroid dehydrogenase 17beta-Hydroxy steroid dehydrogenase 3beta-Hydroxy steroid dehydrogenase

UniprotKB: Accession Number	Entry name	Activity	Subunit	Subcellular location	Cofactor
P19871	3BHD_COMTE	Testosterone + NAD(P)(+) = androst-4-ene-3,17-dione + NAD(P)H.	Homotetramer.

KEGG Pathways
Map code	Pathways	E.C.
MAP00150	Androgen and estrogen metabolism

Compound table
	Substrates			Products				Intermediates
KEGG-id	C00535	C00003	C00006	C00280	C00004	C00005	C00080
E.C.
Compound	testosterone	NAD+	NADP+	androst-4-ene-3,17-dione	NADH	NADPH	H+
Type	carbohydrate,steroid	amide group,amine group,nucleotide	amide group,amine group,nucleotide	carbohydrate,steroid	amide group,amine group,nucleotide	amide group,amine group,nucleotide	others
ChEBI	17347 17347	15846 15846	18009 18009	16422 16422	16908 16908	16474 16474	15378 15378
PubChem	6013 6013	5893 5893	5886 5886	6128 6128	439153 439153	5884 5884	1038 1038

1hxhA00	Unbound	Unbound	Unbound	Unbound	Unbound	Unbound
1hxhB00	Unbound	Unbound	Unbound	Unbound	Unbound	Unbound
1hxhC00	Unbound	Unbound	Unbound	Unbound	Unbound	Unbound
1hxhD00	Unbound	Unbound	Unbound	Unbound	Unbound	Unbound

Reference for Active-site residues
resource	references	E.C.
literature [2], [4]

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

1hxhA00	SER 138;TYR 151;LYS 155
1hxhB00	SER 138;TYR 151;LYS 155
1hxhC00	SER 138;TYR 151;LYS 155
1hxhD00	SER 138;TYR 151;LYS 155

References for Catalytic Mechanism
References	Sections	No. of steps in catalysis
[1]	Fig.1, p.86
[2]	Fig.4, p.38
[3]	Fig.9, Fig.12, Fig.13, p.134-139
[4]	Fig.5, p.14666-14667
[5]	Fig.4, Fig.5, p.25680-25682

References
[1]
Resource
Comments
Medline ID
PubMed ID	2991019
Journal	FEBS Lett
Year	1985
Volume	188
Pages	85-90
Authors	Minard P, Legoy MD, Thomas D
Title	3 beta, 17 beta-hydroxysteroid dehydrogenase of Pseudomonas testosteroni. Kinetic evidence for the bifunctional activity at a common catalytic site.
Related PDB
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID	8993315
Journal	Biochemistry
Year	1997
Volume	36
Pages	34-40
Authors	Oppermann UC, Filling C, Berndt KD, Persson B, Benach J, Ladenstein R, Jornvall H
Title	Active site directed mutagenesis of 3 beta/17 beta-hydroxysteroid dehydrogenase establishes differential effects on short-chain dehydrogenase/reductase reactions.
Related PDB
Related UniProtKB
[3]
Resource
Comments
Medline ID
PubMed ID	10668397
Journal	Vitam Horm
Year	2000
Volume	58
Pages	121-48
Authors	Duax WL, Ghosh D, Pletnev V
Title	Steroid dehydrogenase structures, mechanism of action, and disease.
Related PDB
Related UniProtKB
[4]
Resource
Comments
Medline ID
PubMed ID	12475215
Journal	Biochemistry
Year	2002
Volume	41
Pages	14659-68
Authors	Benach J, Filling C, Oppermann UC, Roversi P, Bricogne G, Berndt KD, Jornvall H, Ladenstein R
Title	Structure of bacterial 3beta/17beta-hydroxysteroid dehydrogenase at 1.2 A resolution: a model for multiple steroid recognition.
Related PDB	1hxh
Related UniProtKB	P19871
[5]
Resource
Comments
Medline ID
PubMed ID	11976334
Journal	J Biol Chem
Year	2002
Volume	277
Pages	25677-84
Authors	Filling C, Berndt KD, Benach J, Knapp S, Prozorovski T, Nordling E, Ladenstein R, Jornvall H, Oppermann U
Title	Critical residues for structure and catalysis in short-chain dehydrogenases/reductases.
Related PDB
Related UniProtKB
[6]
Resource
Comments
Medline ID
PubMed ID	12604210
Journal	Chem Biol Interact
Year	2003
Volume	143-144
Pages	247-53
Authors	Oppermann U, Filling C, Hult M, Shafqat N, Wu X, Lindh M, Shafqat J, Nordling E, Kallberg Y, Persson B, Jornvall H
Title	Short-chain dehydrogenases/reductases (SDR): the 2002 update.
Related PDB
Related UniProtKB

Comments
This enzyme belongs to the short-chain dehydrogenases/reductases(SDR) family. This enzyme catalyzes both the dehydrogenation (oxidation) and reduction of the beta-hydroxyl groups at position-3 and -17 of steroid compounds (see [4]). Thus, this enzyme catalyzes the following reactions, according to the literature [2], [4] and [5]: (A) Hydride transfer from substrate to NAD(P) (Dehydrogenation): (A0) Lys155 modulates the activity (or pKa) of Tyr151 via 2'-hydroxyl group of NAD(P), along with the N1 atom of the nicotinamide group in NAD(P), whereas Ser138 modulates the pKa of hydroxyl oxygen of the substrate. (A1) Tyr151 acts as a general base to deprotonate the hydroxyl oxygen of the substrate. Meanwhile, the hydride transfer occurs from the carbon atom with the hydroxyl group of the substrate to the C4 atom of the nicotinamide. (B) Hydride transfer from NAD(P)H to substrate (Reduction): (B0) Lys155 modulates the activity (or pKa) of Tyr151 via 2'-hydroxyl group of NAD(P)H, along with the N1 atom of the nicotinamide group in NAD(P)H, whereas Ser138 modulates the pKa of carbonyl oxygen of the substrate. (B1) Tyr151 acts as a general acid to protonate the carbonyl oxygen of the substrate. Meanwhile, the hydride transfer occurs from the C4 atom of the nicotinamide to the carbonyl carbon of the substrate. ### According to the literature [5] and [6], the mainchain carbonyl group of Asn111, which is conserved in the superfamily, seems to be involved in proton relay system, by interacting with a water that is also bound to Lys155. However, currently the Asn residue has not been included in the catalytic site in this entry.

Comments

This enzyme belongs to the short-chain dehydrogenases/reductases(SDR) family.
This enzyme catalyzes both the dehydrogenation (oxidation) and reduction of the beta-hydroxyl groups at position-3 and -17 of steroid compounds (see [4]).
Thus, this enzyme catalyzes the following reactions, according to the literature [2], [4] and [5]:
(A) Hydride transfer from substrate to NAD(P) (Dehydrogenation):
(A0) Lys155 modulates the activity (or pKa) of Tyr151 via 2'-hydroxyl group of NAD(P), along with the N1 atom of the nicotinamide group in NAD(P), whereas Ser138 modulates the pKa of hydroxyl oxygen of the substrate.
(A1) Tyr151 acts as a general base to deprotonate the hydroxyl oxygen of the substrate. Meanwhile, the hydride transfer occurs from the carbon atom with the hydroxyl group of the substrate to the C4 atom of the nicotinamide.
(B) Hydride transfer from NAD(P)H to substrate (Reduction):
(B0) Lys155 modulates the activity (or pKa) of Tyr151 via 2'-hydroxyl group of NAD(P)H, along with the N1 atom of the nicotinamide group in NAD(P)H, whereas Ser138 modulates the pKa of carbonyl oxygen of the substrate.
(B1) Tyr151 acts as a general acid to protonate the carbonyl oxygen of the substrate. Meanwhile, the hydride transfer occurs from the C4 atom of the nicotinamide to the carbonyl carbon of the substrate.
###
According to the literature [5] and [6], the mainchain carbonyl group of Asn111, which is conserved in the superfamily, seems to be involved in proton relay system, by interacting with a water that is also bound to Lys155. However, currently the Asn residue has not been included in the catalytic site in this entry.

Created	Updated
2009-01-15	2011-06-17