HSD_MYCTU
ID HSD_MYCTU Reviewed; 260 AA.
AC P9WGT1; L0TB81; P69167; Q10855;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 43.
DE RecName: Full=3-alpha-(or 20-beta)-hydroxysteroid dehydrogenase {ECO:0000305};
DE EC=1.1.1.53 {ECO:0000305|PubMed:12524453};
DE AltName: Full=NADH-dependent 3alpha, 20beta-hydroxysteroid dehydrogenase {ECO:0000303|PubMed:12524453};
GN Name=fabG3; OrderedLocusNames=Rv2002; ORFNames=MTCY39.16c;
OS Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv).
OC Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae;
OC Mycobacterium; Mycobacterium tuberculosis complex.
OX NCBI_TaxID=83332;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=9634230; DOI=10.1038/31159;
RA Cole S.T., Brosch R., Parkhill J., Garnier T., Churcher C.M., Harris D.E.,
RA Gordon S.V., Eiglmeier K., Gas S., Barry C.E. III, Tekaia F., Badcock K.,
RA Basham D., Brown D., Chillingworth T., Connor R., Davies R.M., Devlin K.,
RA Feltwell T., Gentles S., Hamlin N., Holroyd S., Hornsby T., Jagels K.,
RA Krogh A., McLean J., Moule S., Murphy L.D., Oliver S., Osborne J.,
RA Quail M.A., Rajandream M.A., Rogers J., Rutter S., Seeger K., Skelton S.,
RA Squares S., Squares R., Sulston J.E., Taylor K., Whitehead S.,
RA Barrell B.G.;
RT "Deciphering the biology of Mycobacterium tuberculosis from the complete
RT genome sequence.";
RL Nature 393:537-544(1998).
RN [2]
RP SUBUNIT, AND CRYSTALLIZATION OF MUTANT THR-6/MET-47/LYS-69.
RC STRAIN=H37Rv;
RX PubMed=11807257; DOI=10.1107/s0907444901018789;
RA Yang J.K., Yoon H.J., Ahn H.J., Lee B.I., Cho S.H., Waldo G.S., Park M.S.,
RA Suh S.W.;
RT "Crystallization and preliminary X-ray crystallographic analysis of the
RT Rv2002 gene product from Mycobacterium tuberculosis, a beta-ketoacyl
RT carrier protein reductase homologue.";
RL Acta Crystallogr. D 58:303-305(2002).
RN [3]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=21969609; DOI=10.1074/mcp.m111.011627;
RA Kelkar D.S., Kumar D., Kumar P., Balakrishnan L., Muthusamy B., Yadav A.K.,
RA Shrivastava P., Marimuthu A., Anand S., Sundaram H., Kingsbury R.,
RA Harsha H.C., Nair B., Prasad T.S., Chauhan D.S., Katoch K., Katoch V.M.,
RA Kumar P., Chaerkady R., Ramachandran S., Dash D., Pandey A.;
RT "Proteogenomic analysis of Mycobacterium tuberculosis by high resolution
RT mass spectrometry.";
RL Mol. Cell. Proteomics 10:M111.011627-M111.011627(2011).
RN [4] {ECO:0007744|PDB:1NFF, ECO:0007744|PDB:1NFQ, ECO:0007744|PDB:1NFR}
RP X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) OF MUTANT THR-6/MET-47/LYS-69 IN
RP COMPLEXES WITH NAD; NADH AND ANDROSTERONE, FUNCTION, CATALYTIC ACTIVITY,
RP BIOPHYSICOCHEMICAL PROPERTIES, PATHWAY, SUBUNIT, ACTIVE SITE, AND
RP MUTAGENESIS OF ILE-6; VAL-47; THR-69; SER-140 AND TYR-153.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=12524453; DOI=10.1073/pnas.0137017100;
RA Yang J.K., Park M.S., Waldo G.S., Suh S.W.;
RT "Directed evolution approach to a structural genomics project: Rv2002 from
RT Mycobacterium tuberculosis.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:455-460(2003).
CC -!- FUNCTION: Probably involved in steroid metabolism. Catalyzes the
CC oxidation of androsterone (3alpha-hydroxy-5alpha-androstan-17-one) and
CC 20beta-hydroxyprogesterone (4-pregnen-20beta-ol-3-one), and the
CC reduction of progesterone (4-pregnen-3,20-dione). Shows a preference
CC for NADH. Has no detectable activity for oxidation of L-3-
CC hydroxybutyric acid and only an insignificant activity for reduction of
CC acetoacetyl-CoA. {ECO:0000269|PubMed:12524453}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=androstan-3alpha,17beta-diol + NAD(+) = 17beta-
CC hydroxyandrostanone + H(+) + NADH; Xref=Rhea:RHEA:22400,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:18011, ChEBI:CHEBI:57540,
CC ChEBI:CHEBI:57945, ChEBI:CHEBI:85278; EC=1.1.1.53;
CC Evidence={ECO:0000305|PubMed:12524453};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3alpha-hydroxy-5alpha-androstan-17-one + NAD(+) = 5alpha-
CC androstan-3,17-dione + H(+) + NADH; Xref=Rhea:RHEA:20381,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15994, ChEBI:CHEBI:16032,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945;
CC Evidence={ECO:0000269|PubMed:12524453};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:20382;
CC Evidence={ECO:0000269|PubMed:12524453};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(20R)-20-hydroxypregn-4-en-3-one + NAD(+) = H(+) + NADH +
CC progesterone; Xref=Rhea:RHEA:46016, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:17026, ChEBI:CHEBI:36729, ChEBI:CHEBI:57540,
CC ChEBI:CHEBI:57945; Evidence={ECO:0000269|PubMed:12524453};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46017;
CC Evidence={ECO:0000269|PubMed:12524453};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:46018;
CC Evidence={ECO:0000269|PubMed:12524453};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=24 uM for androsterone {ECO:0000269|PubMed:12524453};
CC KM=17 uM for 20beta-hydroxyprogesterone
CC {ECO:0000269|PubMed:12524453};
CC KM=3.3 uM for progesterone {ECO:0000269|PubMed:12524453};
CC Note=kcat is 7.6 min(-1) with androsterone as substrate. kcat is 4.3
CC min(-1) with 20beta-hydroxyprogesterone as substrate. kcat is 1.2
CC min(-1) with progesterone as substrate.
CC {ECO:0000269|PubMed:12524453};
CC pH dependence:
CC Optimum pH is 6.0 for reductase activity.
CC {ECO:0000269|PubMed:12524453};
CC -!- PATHWAY: Lipid metabolism; steroid degradation.
CC {ECO:0000305|PubMed:12524453}.
CC -!- SUBUNIT: Homotetramer (PubMed:12524453). Homodimer (PubMed:11807257).
CC {ECO:0000269|PubMed:11807257, ECO:0000269|PubMed:12524453}.
CC -!- SIMILARITY: Belongs to the short-chain dehydrogenases/reductases (SDR)
CC family. {ECO:0000305}.
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DR EMBL; AL123456; CCP44774.1; -; Genomic_DNA.
DR PIR; H70758; H70758.
DR RefSeq; NP_216518.1; NC_000962.3.
DR RefSeq; WP_003410047.1; NZ_NVQJ01000043.1.
DR PDB; 1NFF; X-ray; 1.80 A; A/B=1-260.
DR PDB; 1NFQ; X-ray; 2.40 A; A/B/C/D=1-260.
DR PDB; 1NFR; X-ray; 2.10 A; A/B/C/D=1-260.
DR PDBsum; 1NFF; -.
DR PDBsum; 1NFQ; -.
DR PDBsum; 1NFR; -.
DR AlphaFoldDB; P9WGT1; -.
DR SMR; P9WGT1; -.
DR STRING; 83332.Rv2002; -.
DR DrugBank; DB02854; Aetiocholanolone.
DR SwissLipids; SLP:000001178; -.
DR PaxDb; P9WGT1; -.
DR DNASU; 888857; -.
DR GeneID; 888857; -.
DR KEGG; mtu:Rv2002; -.
DR TubercuList; Rv2002; -.
DR eggNOG; COG1028; Bacteria.
DR OMA; GICEFKE; -.
DR PhylomeDB; P9WGT1; -.
DR BRENDA; 1.1.1.53; 3445.
DR UniPathway; UPA00722; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005886; C:plasma membrane; HDA:MTBBASE.
DR GO; GO:0047044; F:androstan-3-alpha,17-beta-diol dehydrogenase activity; IDA:MTBBASE.
DR GO; GO:0016616; F:oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor; IBA:GO_Central.
DR GO; GO:0006706; P:steroid catabolic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0008202; P:steroid metabolic process; IDA:MTBBASE.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR020904; Sc_DH/Rdtase_CS.
DR InterPro; IPR002347; SDR_fam.
DR PRINTS; PR00081; GDHRDH.
DR PRINTS; PR00080; SDRFAMILY.
DR SUPFAM; SSF51735; SSF51735; 1.
DR PROSITE; PS00061; ADH_SHORT; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Lipid metabolism; NAD; Oxidoreductase; Reference proteome;
KW Steroid metabolism.
FT CHAIN 1..260
FT /note="3-alpha-(or 20-beta)-hydroxysteroid dehydrogenase"
FT /id="PRO_0000054712"
FT ACT_SITE 153
FT /note="Proton acceptor"
FT /evidence="ECO:0000305|PubMed:12524453"
FT BINDING 17..19
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:12524453,
FT ECO:0007744|PDB:1NFF, ECO:0007744|PDB:1NFQ,
FT ECO:0007744|PDB:1NFR"
FT BINDING 38
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:12524453,
FT ECO:0007744|PDB:1NFF, ECO:0007744|PDB:1NFQ,
FT ECO:0007744|PDB:1NFR"
FT BINDING 61..62
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:12524453,
FT ECO:0007744|PDB:1NFF, ECO:0007744|PDB:1NFQ,
FT ECO:0007744|PDB:1NFR"
FT BINDING 88
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:12524453,
FT ECO:0007744|PDB:1NFF, ECO:0007744|PDB:1NFQ,
FT ECO:0007744|PDB:1NFR"
FT BINDING 153
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:12524453,
FT ECO:0007744|PDB:1NFF, ECO:0007744|PDB:1NFQ,
FT ECO:0007744|PDB:1NFR"
FT BINDING 157
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:12524453,
FT ECO:0007744|PDB:1NFF, ECO:0007744|PDB:1NFQ,
FT ECO:0007744|PDB:1NFR"
FT BINDING 183..191
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:12524453,
FT ECO:0007744|PDB:1NFF, ECO:0007744|PDB:1NFQ,
FT ECO:0007744|PDB:1NFR"
FT MUTAGEN 6
FT /note="I->T: Maximal improvement in solubility; when
FT associated with M-47 and K-69."
FT /evidence="ECO:0000269|PubMed:12524453"
FT MUTAGEN 47
FT /note="V->M: Maximal improvement in solubility; when
FT associated with T-6 and K-69."
FT /evidence="ECO:0000269|PubMed:12524453"
FT MUTAGEN 69
FT /note="T->K: Maximal improvement in solubility; when
FT associated with T-6 and M-47."
FT /evidence="ECO:0000269|PubMed:12524453"
FT MUTAGEN 140
FT /note="S->A: Complete loss of both oxidation of
FT androsterone and reduction of progesterone; when associated
FT with T6; M-47 and K-69."
FT /evidence="ECO:0000269|PubMed:12524453"
FT MUTAGEN 153
FT /note="Y->F: Complete loss of both oxidation of
FT androsterone and reduction of progesterone; when associated
FT with T6; M-47 and K-69."
FT /evidence="ECO:0000269|PubMed:12524453"
FT TURN 4..7
FT /evidence="ECO:0007829|PDB:1NFF"
FT STRAND 9..13
FT /evidence="ECO:0007829|PDB:1NFF"
FT TURN 14..16
FT /evidence="ECO:0007829|PDB:1NFF"
FT HELIX 18..29
FT /evidence="ECO:0007829|PDB:1NFF"
FT STRAND 33..39
FT /evidence="ECO:0007829|PDB:1NFF"
FT HELIX 41..50
FT /evidence="ECO:0007829|PDB:1NFF"
FT HELIX 52..54
FT /evidence="ECO:0007829|PDB:1NFF"
FT STRAND 55..59
FT /evidence="ECO:0007829|PDB:1NFF"
FT HELIX 65..79
FT /evidence="ECO:0007829|PDB:1NFF"
FT STRAND 84..87
FT /evidence="ECO:0007829|PDB:1NFF"
FT TURN 97..99
FT /evidence="ECO:0007829|PDB:1NFF"
FT HELIX 102..112
FT /evidence="ECO:0007829|PDB:1NFF"
FT HELIX 114..130
FT /evidence="ECO:0007829|PDB:1NFF"
FT STRAND 133..138
FT /evidence="ECO:0007829|PDB:1NFF"
FT HELIX 141..143
FT /evidence="ECO:0007829|PDB:1NFF"
FT HELIX 151..171
FT /evidence="ECO:0007829|PDB:1NFF"
FT HELIX 172..174
FT /evidence="ECO:0007829|PDB:1NFF"
FT STRAND 176..183
FT /evidence="ECO:0007829|PDB:1NFF"
FT HELIX 189..191
FT /evidence="ECO:0007829|PDB:1NFF"
FT STRAND 202..205
FT /evidence="ECO:0007829|PDB:1NFF"
FT HELIX 209..220
FT /evidence="ECO:0007829|PDB:1NFF"
FT HELIX 222..224
FT /evidence="ECO:0007829|PDB:1NFF"
FT STRAND 231..235
FT /evidence="ECO:0007829|PDB:1NFF"
FT HELIX 238..240
FT /evidence="ECO:0007829|PDB:1NFF"
SQ SEQUENCE 260 AA; 27030 MW; 0935A14ED36220B7 CRC64;
MSGRLIGKVA LVSGGARGMG ASHVRAMVAE GAKVVFGDIL DEEGKAVAAE LADAARYVHL
DVTQPAQWTA AVDTAVTAFG GLHVLVNNAG ILNIGTIEDY ALTEWQRILD VNLTGVFLGI
RAVVKPMKEA GRGSIINISS IEGLAGTVAC HGYTATKFAV RGLTKSTALE LGPSGIRVNS
IHPGLVKTPM TDWVPEDIFQ TALGRAAEPV EVSNLVVYLA SDESSYSTGA EFVVDGGTVA
GLAHNDFGAV EVSSQPEWVT
