LTP2_THECD
ID LTP2_THECD Reviewed; 391 AA.
AC D1AB74;
DT 07-APR-2021, integrated into UniProtKB/Swiss-Prot.
DT 19-JAN-2010, sequence version 1.
DT 25-MAY-2022, entry version 55.
DE RecName: Full=Steroid side-chain-cleaving aldolase {ECO:0000305};
DE EC=4.1.3.- {ECO:0000269|PubMed:31209106};
DE AltName: Full=3-oxo-23,24-bisnorchol-4-en-17-ol-22-oyl-CoA lyase {ECO:0000305};
GN Name=ltp2 {ECO:0000303|PubMed:31209106};
GN OrderedLocusNames=Tcur_3479 {ECO:0000312|EMBL:ACY99017.1};
OS Thermomonospora curvata (strain ATCC 19995 / DSM 43183 / JCM 3096 / KCTC
OS 9072 / NBRC 15933 / NCIMB 10081 / Henssen B9).
OC Bacteria; Actinobacteria; Streptosporangiales; Thermomonosporaceae;
OC Thermomonospora.
OX NCBI_TaxID=471852;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 19995 / DSM 43183 / JCM 3096 / KCTC 9072 / NBRC 15933 / NCIMB
RC 10081 / Henssen B9;
RX PubMed=21475583; DOI=10.4056/sigs.1453580;
RA Chertkov O., Sikorski J., Nolan M., Lapidus A., Lucas S., Del Rio T.G.,
RA Tice H., Cheng J.F., Goodwin L., Pitluck S., Liolios K., Ivanova N.,
RA Mavromatis K., Mikhailova N., Ovchinnikova G., Pati A., Chen A.,
RA Palaniappan K., Djao O.D., Land M., Hauser L., Chang Y.J., Jeffries C.D.,
RA Brettin T., Han C., Detter J.C., Rohde M., Goeker M., Woyke T., Bristow J.,
RA Eisen J.A., Markowitz V., Hugenholtz P., Klenk H.P., Kyrpides N.C.;
RT "Complete genome sequence of Thermomonospora curvata type strain (B9).";
RL Stand. Genomic Sci. 1:13-22(2011).
RN [2] {ECO:0007744|PDB:6OK1}
RP X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS) IN COMPLEX WITH CHSH2-DUF35,
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT,
RP INTERACTION WITH CHSH2, ACTIVE SITE, AND MUTAGENESIS OF GLY-82; TYR-294;
RP HIS-296; TYR-344 AND HIS-346.
RC STRAIN=ATCC 19995 / DSM 43183 / JCM 3096 / KCTC 9072 / NBRC 15933 / NCIMB
RC 10081 / Henssen B9;
RX PubMed=31209106; DOI=10.1074/jbc.ra119.008889;
RA Aggett R., Mallette E., Gilbert S.E., Vachon M.A., Schroeter K.L.,
RA Kimber M.S., Seah S.Y.K.;
RT "The steroid side-chain-cleaving aldolase Ltp2-ChsH2DUF35 is a thiolase
RT superfamily member with a radically repurposed active site.";
RL J. Biol. Chem. 294:11934-11943(2019).
CC -!- FUNCTION: Probably involved in bile acid degradation (Probable). In
CC vitro, when associated with the ChsH1/ChsH2 hydratase, catalyzes the
CC retroaldol cleavage of 17-hydroxy-3-oxo-4-pregnene-20-carboxyl-CoA (17-
CC HOPC-CoA), forming androst-4-ene-3,17-dione and propionyl-CoA
CC (PubMed:31209106). The in vivo substrate is probably a closely
CC analogous bile acid degradation metabolite (Probable).
CC {ECO:0000269|PubMed:31209106, ECO:0000305|PubMed:31209106}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=17-hydroxy-3-oxochol-4-en-22-oyl-CoA = androst-4-ene-3,17-
CC dione + propanoyl-CoA; Xref=Rhea:RHEA:46648, ChEBI:CHEBI:16422,
CC ChEBI:CHEBI:57392, ChEBI:CHEBI:86028;
CC Evidence={ECO:0000269|PubMed:31209106};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=2.4 uM for 17-HOPC-CoA (in the presence of ChsH2-DUF35)
CC {ECO:0000269|PubMed:31209106};
CC Note=kcat is 7.1 sec(-1). {ECO:0000269|PubMed:31209106};
CC -!- SUBUNIT: Homodimer (PubMed:31209106). Interacts with the ChsH1/ChsH2
CC hydratase via the DUF35 C-terminal region of ChsH2 (ChsH2-DUF35)
CC (PubMed:31209106). {ECO:0000269|PubMed:31209106}.
CC -!- SIMILARITY: Belongs to the thiolase-like superfamily. {ECO:0000305}.
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DR EMBL; CP001738; ACY99017.1; -; Genomic_DNA.
DR RefSeq; WP_012853801.1; NC_013510.1.
DR PDB; 6OK1; X-ray; 1.70 A; A/C=1-391.
DR PDBsum; 6OK1; -.
DR AlphaFoldDB; D1AB74; -.
DR SMR; D1AB74; -.
DR STRING; 471852.Tcur_3479; -.
DR EnsemblBacteria; ACY99017; ACY99017; Tcur_3479.
DR KEGG; tcu:Tcur_3479; -.
DR eggNOG; COG0183; Bacteria.
DR HOGENOM; CLU_035425_2_0_11; -.
DR OMA; FMAHYAP; -.
DR OrthoDB; 647502at2; -.
DR Proteomes; UP000001918; Chromosome.
DR GO; GO:0016747; F:acyltransferase activity, transferring groups other than amino-acyl groups; IEA:InterPro.
DR GO; GO:0016829; F:lyase activity; IEA:UniProtKB-KW.
DR GO; GO:0030573; P:bile acid catabolic process; IEA:UniProtKB-KW.
DR GO; GO:0016042; P:lipid catabolic process; IEA:UniProtKB-KW.
DR Gene3D; 3.40.47.10; -; 1.
DR InterPro; IPR002155; Thiolase.
DR InterPro; IPR016039; Thiolase-like.
DR InterPro; IPR020616; Thiolase_N.
DR Pfam; PF00108; Thiolase_N; 1.
DR PIRSF; PIRSF000429; Ac-CoA_Ac_transf; 1.
DR SUPFAM; SSF53901; SSF53901; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Bile acid catabolism; Lipid degradation; Lipid metabolism;
KW Lyase; Reference proteome; Steroid metabolism.
FT CHAIN 1..391
FT /note="Steroid side-chain-cleaving aldolase"
FT /id="PRO_0000452244"
FT ACT_SITE 294
FT /note="Proton acceptor"
FT /evidence="ECO:0000305|PubMed:31209106"
FT ACT_SITE 344
FT /note="Proton donor"
FT /evidence="ECO:0000305|PubMed:31209106"
FT MUTAGEN 82
FT /note="G->P: Almost loss of activity."
FT /evidence="ECO:0000269|PubMed:31209106"
FT MUTAGEN 294
FT /note="Y->F: Almost loss of activity. Loss of activity;
FT when associated with F-344."
FT /evidence="ECO:0000269|PubMed:31209106"
FT MUTAGEN 296
FT /note="H->A: 13-fold decrease in catalytic efficiency."
FT /evidence="ECO:0000269|PubMed:31209106"
FT MUTAGEN 344
FT /note="Y->F: 322-fold decrease in catalytic efficiency.
FT Loss of activity; when associated with F-294."
FT /evidence="ECO:0000269|PubMed:31209106"
FT MUTAGEN 346
FT /note="H->A: 11-fold decrease in catalytic efficiency."
FT /evidence="ECO:0000269|PubMed:31209106"
FT TURN 5..7
FT /evidence="ECO:0007829|PDB:6OK1"
FT STRAND 8..15
FT /evidence="ECO:0007829|PDB:6OK1"
FT HELIX 26..40
FT /evidence="ECO:0007829|PDB:6OK1"
FT HELIX 45..47
FT /evidence="ECO:0007829|PDB:6OK1"
FT STRAND 50..54
FT /evidence="ECO:0007829|PDB:6OK1"
FT HELIX 61..68
FT /evidence="ECO:0007829|PDB:6OK1"
FT STRAND 73..79
FT /evidence="ECO:0007829|PDB:6OK1"
FT HELIX 82..85
FT /evidence="ECO:0007829|PDB:6OK1"
FT HELIX 86..98
FT /evidence="ECO:0007829|PDB:6OK1"
FT STRAND 103..112
FT /evidence="ECO:0007829|PDB:6OK1"
FT TURN 113..115
FT /evidence="ECO:0007829|PDB:6OK1"
FT HELIX 132..135
FT /evidence="ECO:0007829|PDB:6OK1"
FT HELIX 136..139
FT /evidence="ECO:0007829|PDB:6OK1"
FT HELIX 141..143
FT /evidence="ECO:0007829|PDB:6OK1"
FT HELIX 148..163
FT /evidence="ECO:0007829|PDB:6OK1"
FT HELIX 167..182
FT /evidence="ECO:0007829|PDB:6OK1"
FT TURN 188..191
FT /evidence="ECO:0007829|PDB:6OK1"
FT HELIX 196..201
FT /evidence="ECO:0007829|PDB:6OK1"
FT STRAND 204..207
FT /evidence="ECO:0007829|PDB:6OK1"
FT HELIX 211..213
FT /evidence="ECO:0007829|PDB:6OK1"
FT STRAND 219..228
FT /evidence="ECO:0007829|PDB:6OK1"
FT HELIX 229..232
FT /evidence="ECO:0007829|PDB:6OK1"
FT STRAND 235..237
FT /evidence="ECO:0007829|PDB:6OK1"
FT STRAND 240..249
FT /evidence="ECO:0007829|PDB:6OK1"
FT HELIX 268..281
FT /evidence="ECO:0007829|PDB:6OK1"
FT HELIX 285..287
FT /evidence="ECO:0007829|PDB:6OK1"
FT STRAND 290..292
FT /evidence="ECO:0007829|PDB:6OK1"
FT STRAND 296..298
FT /evidence="ECO:0007829|PDB:6OK1"
FT HELIX 301..307
FT /evidence="ECO:0007829|PDB:6OK1"
FT HELIX 316..321
FT /evidence="ECO:0007829|PDB:6OK1"
FT TURN 322..325
FT /evidence="ECO:0007829|PDB:6OK1"
FT STRAND 329..331
FT /evidence="ECO:0007829|PDB:6OK1"
FT HELIX 338..341
FT /evidence="ECO:0007829|PDB:6OK1"
FT HELIX 348..359
FT /evidence="ECO:0007829|PDB:6OK1"
FT STRAND 370..375
FT /evidence="ECO:0007829|PDB:6OK1"
FT STRAND 378..388
FT /evidence="ECO:0007829|PDB:6OK1"
SQ SEQUENCE 391 AA; 41404 MW; FEE8D313CF0D8894 CRC64;
MSVLPGAAAI AGIGATEFSK NSGRSELQLA CEAVLAAIAD AGLEPSDVDG LVTFTADTSS
EIHVARNTGI GELKFFSRVG YGGGAACGTV QQAAMAVATG IAEVVVCYRA FNERSGVRYG
LGQAGRQMDQ GADSAAYAWL LPFGLNTPAQ WVAMFARRYM HEYGATSEDF GRVAVVDRKH
AATNPKAWFY QRPITLEDHQ NSRWIVEPLH LLDCCQESDG GQALVVVSTE RARDLPHPPA
LIWGAAQGSG YDQHMMTSYY RSEITGIPEM GLVGQQLYAQ SGLNPSDIGA AILYDHFTPL
VLPQLEELGF CARGEAKDFI ADGNLEIGGR LPCNTHGGQL GEAYIHGMNG IAEAVRLVRG
TSVNQPGDVT NVLVTAGTGV PTSGLILGAD R
