FADB2_MYCTU
ID FADB2_MYCTU Reviewed; 286 AA.
AC P9WNP7; L0T3U3; O53753; Q7D9R6;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 41.
DE RecName: Full=3-hydroxybutyryl-CoA dehydrogenase;
DE EC=1.1.1.157 {ECO:0000269|PubMed:20378648};
DE AltName: Full=Beta-hydroxybutyryl-CoA dehydrogenase;
DE Short=BHBD;
GN Name=fadB2; OrderedLocusNames=Rv0468;
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 INDUCTION.
RX PubMed=11489128; DOI=10.1046/j.1365-2958.2001.02525.x;
RA Manganelli R., Voskuil M.I., Schoolnik G.K., Smith I.;
RT "The Mycobacterium tuberculosis ECF sigma factor sigmaE: role in global
RT gene expression and survival in macrophages.";
RL Mol. Microbiol. 41:423-437(2001).
RN [3]
RP INDUCTION.
RX PubMed=12081975; DOI=10.1128/jb.184.14.4025-4032.2002;
RA Fisher M.A., Plikaytis B.B., Shinnick T.M.;
RT "Microarray analysis of the Mycobacterium tuberculosis transcriptional
RT response to the acidic conditions found in phagosomes.";
RL J. Bacteriol. 184:4025-4032(2002).
RN [4]
RP FUNCTION AS A 3-HYDROXYBUTYRYL-COA DEHYDROGENASE, CATALYTIC ACTIVITY,
RP MUTAGENESIS OF SER-122, ACTIVITY REGULATION, AND BIOPHYSICOCHEMICAL
RP PROPERTIES.
RX PubMed=20378648; DOI=10.1099/mic.0.038802-0;
RA Taylor R.C., Brown A.K., Singh A., Bhatt A., Besra G.S.;
RT "Characterization of a beta-hydroxybutyryl-CoA dehydrogenase from
RT Mycobacterium tuberculosis.";
RL Microbiology 156:1975-1982(2010).
RN [5]
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).
CC -!- FUNCTION: Catalyzes the NAD-dependent oxidation of beta-hydroxybutyryl-
CC CoA to acetoacetyl-CoA in vitro at pH 10. Also catalyzes the reverse
CC reaction albeit in a lower pH range of 5.5-6.5. The reverse reaction is
CC able to use NADPH as well as NADH. {ECO:0000269|PubMed:20378648}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3-hydroxybutanoyl-CoA + NAD(+) = acetoacetyl-CoA + H(+) +
CC NADH; Xref=Rhea:RHEA:42048, ChEBI:CHEBI:15378, ChEBI:CHEBI:57286,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:78611;
CC Evidence={ECO:0000269|PubMed:20378648};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42049;
CC Evidence={ECO:0000269|PubMed:20378648};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:42050;
CC Evidence={ECO:0000269|PubMed:20378648};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(3S)-3-hydroxybutanoyl-CoA + NADP(+) = acetoacetyl-CoA + H(+)
CC + NADPH; Xref=Rhea:RHEA:16197, ChEBI:CHEBI:15378, ChEBI:CHEBI:57286,
CC ChEBI:CHEBI:57316, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349;
CC EC=1.1.1.157; Evidence={ECO:0000269|PubMed:20378648};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:16199;
CC Evidence={ECO:0000269|PubMed:20378648};
CC -!- ACTIVITY REGULATION: Activated by magnesium and calcium, and inhibited
CC by zinc, nickel and cobalt. {ECO:0000269|PubMed:20378648}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=29.5 mM for NAD (at pH 9.5 and at 30 degrees Celsius)
CC {ECO:0000269|PubMed:20378648};
CC KM=43.5 mM for beta-hydroxybutyryl-CoA (at pH 9.5 and at 30 degrees
CC Celsius) {ECO:0000269|PubMed:20378648};
CC KM=50.0 mM for NADH (at pH 9.5 and at 30 degrees Celsius)
CC {ECO:0000269|PubMed:20378648};
CC KM=65.6 mM for acetoacetyl-CoA (at pH 9.5 and at 30 degrees Celsius)
CC {ECO:0000269|PubMed:20378648};
CC Vmax=63.1 nmol/min/mg enzyme with NAD as substrate (at pH 9.5 and at
CC 30 degrees Celsius) {ECO:0000269|PubMed:20378648};
CC Vmax=126.6 nmol/min/mg enzyme with acetoacetyl-CoA as substrate (at
CC pH 9.5 and at 30 degrees Celsius) {ECO:0000269|PubMed:20378648};
CC Vmax=188.3 nmol/min/mg enzyme with beta-hydroxybutyryl-CoA as
CC substrate (at pH 9.5 and at 30 degrees Celsius)
CC {ECO:0000269|PubMed:20378648};
CC Vmax=2588.0 nmol/min/mg enzyme with NADH as substrate (at pH 9.5 and
CC at 30 degrees Celsius) {ECO:0000269|PubMed:20378648};
CC pH dependence:
CC Optimum pH is 10. {ECO:0000269|PubMed:20378648};
CC Temperature dependence:
CC Optimum temperature is 37 degrees Celsius.
CC {ECO:0000269|PubMed:20378648};
CC -!- PATHWAY: Lipid metabolism; butanoate metabolism.
CC -!- INDUCTION: Up-regulated upon acid shock and SDS stress.
CC {ECO:0000269|PubMed:11489128, ECO:0000269|PubMed:12081975}.
CC -!- SIMILARITY: Belongs to the 3-hydroxyacyl-CoA dehydrogenase family.
CC {ECO:0000305}.
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DR EMBL; AL123456; CCP43201.1; -; Genomic_DNA.
DR PIR; H70828; H70828.
DR RefSeq; NP_214982.1; NC_000962.3.
DR RefSeq; WP_003402318.1; NZ_NVQJ01000002.1.
DR PDB; 6HRD; X-ray; 2.11 A; A/B/C/D/E/F=1-286.
DR PDBsum; 6HRD; -.
DR AlphaFoldDB; P9WNP7; -.
DR SMR; P9WNP7; -.
DR BioGRID; 4355762; 1.
DR STRING; 83332.Rv0468; -.
DR SwissLipids; SLP:000001179; -.
DR PaxDb; P9WNP7; -.
DR DNASU; 886288; -.
DR GeneID; 45424430; -.
DR GeneID; 886288; -.
DR KEGG; mtu:Rv0468; -.
DR TubercuList; Rv0468; -.
DR eggNOG; COG1250; Bacteria.
DR OMA; SVMEVFY; -.
DR PhylomeDB; P9WNP7; -.
DR BRENDA; 1.1.1.35; 3445.
DR UniPathway; UPA00863; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005829; C:cytosol; HDA:MTBBASE.
DR GO; GO:0009274; C:peptidoglycan-based cell wall; HDA:MTBBASE.
DR GO; GO:0005886; C:plasma membrane; HDA:MTBBASE.
DR GO; GO:0008691; F:3-hydroxybutyryl-CoA dehydrogenase activity; IDA:MTBBASE.
DR GO; GO:0070403; F:NAD+ binding; IEA:InterPro.
DR GO; GO:0016491; F:oxidoreductase activity; IBA:GO_Central.
DR GO; GO:0019605; P:butyrate metabolic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0006635; P:fatty acid beta-oxidation; IDA:MTBBASE.
DR GO; GO:0030497; P:fatty acid elongation; IDA:MTBBASE.
DR GO; GO:0052572; P:response to host immune response; IEP:MTBBASE.
DR Gene3D; 1.10.1040.10; -; 1.
DR InterPro; IPR022694; 3-OHacyl-CoA_DH.
DR InterPro; IPR006176; 3-OHacyl-CoA_DH_NAD-bd.
DR InterPro; IPR006108; 3HC_DH_C.
DR InterPro; IPR008927; 6-PGluconate_DH-like_C_sf.
DR InterPro; IPR013328; 6PGD_dom2.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR Pfam; PF00725; 3HCDH; 1.
DR Pfam; PF02737; 3HCDH_N; 1.
DR PIRSF; PIRSF000105; HCDH; 1.
DR SUPFAM; SSF48179; SSF48179; 1.
DR SUPFAM; SSF51735; SSF51735; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Fatty acid metabolism; Lipid metabolism; NADP;
KW Oxidoreductase; Reference proteome.
FT CHAIN 1..286
FT /note="3-hydroxybutyryl-CoA dehydrogenase"
FT /id="PRO_0000403378"
FT SITE 143
FT /note="Important for catalytic activity"
FT /evidence="ECO:0000250"
FT MUTAGEN 122
FT /note="S->A: Loss of fatty acyl dehydrogenase activity."
FT /evidence="ECO:0000269|PubMed:20378648"
FT STRAND 7..11
FT /evidence="ECO:0007829|PDB:6HRD"
FT HELIX 15..26
FT /evidence="ECO:0007829|PDB:6HRD"
FT STRAND 30..34
FT /evidence="ECO:0007829|PDB:6HRD"
FT HELIX 38..57
FT /evidence="ECO:0007829|PDB:6HRD"
FT HELIX 63..71
FT /evidence="ECO:0007829|PDB:6HRD"
FT STRAND 73..77
FT /evidence="ECO:0007829|PDB:6HRD"
FT HELIX 79..82
FT /evidence="ECO:0007829|PDB:6HRD"
FT STRAND 86..90
FT /evidence="ECO:0007829|PDB:6HRD"
FT HELIX 96..109
FT /evidence="ECO:0007829|PDB:6HRD"
FT STRAND 116..119
FT /evidence="ECO:0007829|PDB:6HRD"
FT STRAND 122..124
FT /evidence="ECO:0007829|PDB:6HRD"
FT HELIX 126..130
FT /evidence="ECO:0007829|PDB:6HRD"
FT HELIX 136..138
FT /evidence="ECO:0007829|PDB:6HRD"
FT STRAND 139..143
FT /evidence="ECO:0007829|PDB:6HRD"
FT TURN 148..150
FT /evidence="ECO:0007829|PDB:6HRD"
FT STRAND 153..157
FT /evidence="ECO:0007829|PDB:6HRD"
FT HELIX 164..176
FT /evidence="ECO:0007829|PDB:6HRD"
FT STRAND 181..185
FT /evidence="ECO:0007829|PDB:6HRD"
FT TURN 189..192
FT /evidence="ECO:0007829|PDB:6HRD"
FT HELIX 193..209
FT /evidence="ECO:0007829|PDB:6HRD"
FT HELIX 215..226
FT /evidence="ECO:0007829|PDB:6HRD"
FT HELIX 232..239
FT /evidence="ECO:0007829|PDB:6HRD"
FT HELIX 241..255
FT /evidence="ECO:0007829|PDB:6HRD"
FT HELIX 258..260
FT /evidence="ECO:0007829|PDB:6HRD"
FT HELIX 264..272
FT /evidence="ECO:0007829|PDB:6HRD"
FT HELIX 277..279
FT /evidence="ECO:0007829|PDB:6HRD"
FT STRAND 281..285
FT /evidence="ECO:0007829|PDB:6HRD"
SQ SEQUENCE 286 AA; 30728 MW; F1A490B88BCB026B CRC64;
MSDAIQRVGV VGAGQMGSGI AEVSARAGVE VTVFEPAEAL ITAGRNRIVK SLERAVSAGK
VTERERDRAL GLLTFTTDLN DLSDRQLVIE AVVEDEAVKS EIFAELDRVV TDPDAVLASN
TSSIPIMKVA AATKQPQRVL GLHFFNPVPV LPLVELVRTL VTDEAAAART EEFASTVLGK
QVVRCSDRSG FVVNALLVPY LLSAIRMVEA GFATVEDVDK AVVAGLSHPM GPLRLSDLVG
LDTLKLIADK MFEEFKEPHY GPPPLLLRMV EAGQLGKKSG RGFYTY
