ID   CAR_SEGRC               Reviewed;        1188 AA.
AC   E5XP76;
DT   02-JUN-2021, integrated into UniProtKB/Swiss-Prot.
DT   08-MAR-2011, sequence version 1.
DT   02-JUN-2021, entry version 61.
DE   RecName: Full=Carboxylic acid reductase {ECO:0000255|HAMAP-Rule:MF_02247, ECO:0000303|PubMed:28719588};
DE            Short=CAR {ECO:0000255|HAMAP-Rule:MF_02247, ECO:0000303|PubMed:28719588};
DE            EC=1.2.1.- {ECO:0000255|HAMAP-Rule:MF_02247, ECO:0000269|PubMed:28719588};
DE   AltName: Full=ATP/NADPH-dependent carboxylic acid reductase {ECO:0000255|HAMAP-Rule:MF_02247, ECO:0000305};
GN   Name=car {ECO:0000255|HAMAP-Rule:MF_02247};
GN   ORFNames=HMPREF9336_01297 {ECO:0000312|EMBL:EFV13858.1};
OS   Segniliparus rugosus (strain ATCC BAA-974 / DSM 45345 / CCUG 50838 / CIP
OS   108380 / JCM 13579 / CDC 945).
OC   Bacteria; Actinobacteria; Corynebacteriales; Segniliparaceae; Segniliparus.
OX   NCBI_TaxID=679197;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC BAA-974 / DSM 45345 / CCUG 50838 / CIP 108380 / JCM 13579 / CDC
RC   945;
RX   PubMed=22675588; DOI=10.4056/sigs.2255041;
RA   Earl A.M., Desjardins C.A., Fitzgerald M.G., Arachchi H.M., Zeng Q.,
RA   Mehta T., Griggs A., Birren B.W., Toney N.C., Carr J., Posey J.,
RA   Butler W.R.;
RT   "High quality draft genome sequence of Segniliparus rugosus CDC 945(T)=
RT   (ATCC BAA-974(T)).";
RL   Stand. Genomic Sci. 5:389-397(2011).
RN   [2] {ECO:0007744|PDB:5MSP, ECO:0007744|PDB:5MSR, ECO:0007744|PDB:5MSS, ECO:0007744|PDB:5MST, ECO:0007744|PDB:5MSV, ECO:0007744|PDB:5MSW}
RP   X-RAY CRYSTALLOGRAPHY (1.72 ANGSTROMS) IN COMPLEXES WITH AMP; NADP AND
RP   PHOSPHOPANTETHEINE, FUNCTION, CATALYTIC ACTIVITY, COFACTOR, DOMAIN,
RP   PHOSPHOPANTETHEINYLATION AT SER-702, AND MUTAGENESIS OF HIS-900; TYR-966;
RP   ASP-998; GLN-1015; ARG-1018 AND LEU-1131.
RX   PubMed=28719588; DOI=10.1038/nchembio.2434;
RA   Gahloth D., Dunstan M.S., Quaglia D., Klumbys E., Lockhart-Cairns M.P.,
RA   Hill A.M., Derrington S.R., Scrutton N.S., Turner N.J., Leys D.;
RT   "Structures of carboxylic acid reductase reveal domain dynamics underlying
RT   catalysis.";
RL   Nat. Chem. Biol. 13:975-981(2017).
CC   -!- FUNCTION: Catalyzes the ATP- and NADPH-dependent reduction of
CC       carboxylic acids to the corresponding aldehydes (PubMed:28719588).
CC       Catalyzes the reduction of a very wide range of carboxylic acids,
CC       including benzoic acids, heterocyclic, phenylacetic, phenylpropanoic
CC       and fatty acid substrates (PubMed:28719588).
CC       {ECO:0000269|PubMed:28719588}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=a carboxylate + ATP + H(+) + NADPH = AMP + an aldehyde +
CC         diphosphate + NADP(+); Xref=Rhea:RHEA:50916, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:17478, ChEBI:CHEBI:29067, ChEBI:CHEBI:30616,
CC         ChEBI:CHEBI:33019, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349,
CC         ChEBI:CHEBI:456215; Evidence={ECO:0000255|HAMAP-Rule:MF_02247,
CC         ECO:0000269|PubMed:28719588};
CC   -!- COFACTOR:
CC       Name=pantetheine 4'-phosphate; Xref=ChEBI:CHEBI:47942;
CC         Evidence={ECO:0000255|HAMAP-Rule:MF_02247,
CC         ECO:0000269|PubMed:28719588};
CC       Note=Binds 1 phosphopantetheine covalently. {ECO:0000255|HAMAP-
CC       Rule:MF_02247, ECO:0000269|PubMed:28719588};
CC   -!- DOMAIN: The N-terminal domain likely catalyzes substrate activation by
CC       formation of an initial acyl-AMP intermediate, the central region
CC       contains the phosphopantetheine attachment site, and the C-terminal
CC       domain catalyzes the reduction by NADPH of the intermediate thioester
CC       formed from the attack of the phosphopantetheine thiol at the carbonyl
CC       carbon of acyl-AMP (By similarity). Large-scale domain motions occur
CC       between the adenylation and thiolation states. Phosphopantetheine
CC       binding alters the orientation of a key Asp, resulting in a productive
CC       orientation of the bound nicotinamide. This ensures that further
CC       reduction of the aldehyde product does not occur (PubMed:28719588).
CC       {ECO:0000250|UniProtKB:Q6RKB1, ECO:0000269|PubMed:28719588}.
CC   -!- SIMILARITY: Belongs to the ATP-dependent AMP-binding enzyme family.
CC       Carboxylic acid reductase subfamily. {ECO:0000255|HAMAP-Rule:MF_02247,
CC       ECO:0000305}.
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DR   EMBL; ACZI02000003; EFV13858.1; -; Genomic_DNA.
DR   RefSeq; WP_007468889.1; NZ_KI391954.1.
DR   PDB; 5MSP; X-ray; 2.41 A; A=1-1188.
DR   PDB; 5MSR; X-ray; 2.37 A; A/B/C/D=1-1188.
DR   PDB; 5MSS; X-ray; 1.96 A; A=1-1188.
DR   PDB; 5MST; X-ray; 1.72 A; A/B=1-1188.
DR   PDB; 5MSV; X-ray; 2.34 A; A/B/C/D=1-1188.
DR   PDB; 5MSW; X-ray; 2.33 A; A=1-1188.
DR   PDBsum; 5MSP; -.
DR   PDBsum; 5MSR; -.
DR   PDBsum; 5MSS; -.
DR   PDBsum; 5MST; -.
DR   PDBsum; 5MSV; -.
DR   PDBsum; 5MSW; -.
DR   SMR; E5XP76; -.
DR   STRING; 679197.HMPREF9336_01297; -.
DR   EnsemblBacteria; EFV13858; EFV13858; HMPREF9336_01297.
DR   eggNOG; COG0236; Bacteria.
DR   eggNOG; COG1022; Bacteria.
DR   eggNOG; COG3320; Bacteria.
DR   HOGENOM; CLU_009549_0_0_11; -.
DR   OrthoDB; 572620at2; -.
DR   Proteomes; UP000004816; Unassembled WGS sequence.
DR   GO; GO:0031177; F:phosphopantetheine binding; IEA:InterPro.
DR   CDD; cd05235; SDR_e1; 1.
DR   Gene3D; 1.10.1200.10; -; 1.
DR   Gene3D; 3.40.50.12780; -; 1.
DR   HAMAP; MF_02247; Carbox_acid_reduct; 1.
DR   InterPro; IPR036736; ACP-like_sf.
DR   InterPro; IPR020845; AMP-binding_CS.
DR   InterPro; IPR000873; AMP-dep_Synth/Lig.
DR   InterPro; IPR042099; AMP-dep_Synthh-like_sf.
DR   InterPro; IPR013120; Far_NAD-bd.
DR   InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR   InterPro; IPR020806; PKS_PP-bd.
DR   InterPro; IPR009081; PP-bd_ACP.
DR   InterPro; IPR010080; Thioester_reductase-like_dom.
DR   Pfam; PF00501; AMP-binding; 1.
DR   Pfam; PF07993; NAD_binding_4; 1.
DR   Pfam; PF00550; PP-binding; 1.
DR   SMART; SM00823; PKS_PP; 1.
DR   SUPFAM; SSF47336; SSF47336; 1.
DR   SUPFAM; SSF51735; SSF51735; 1.
DR   TIGRFAMs; TIGR01746; Thioester-redct; 1.
DR   PROSITE; PS00455; AMP_BINDING; 1.
DR   PROSITE; PS50075; CARRIER; 1.
PE   1: Evidence at protein level;
KW   3D-structure; ATP-binding; NADP; Nucleotide-binding; Oxidoreductase;
KW   Phosphopantetheine; Phosphoprotein.
FT   CHAIN           1..1188
FT                   /note="Carboxylic acid reductase"
FT                   /id="PRO_0000452836"
FT   DOMAIN          665..743
FT                   /note="Carrier"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_02247"
FT   NP_BIND         429..430
FT                   /note="AMP"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_02247,
FT                   ECO:0000269|PubMed:28719588, ECO:0007744|PDB:5MSS,
FT                   ECO:0007744|PDB:5MST, ECO:0007744|PDB:5MSW"
FT   NP_BIND         519..522
FT                   /note="AMP"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_02247,
FT                   ECO:0000269|PubMed:28719588, ECO:0007744|PDB:5MST,
FT                   ECO:0007744|PDB:5MSW"
FT   NP_BIND         801..804
FT                   /note="NADP"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_02247,
FT                   ECO:0000269|PubMed:28719588, ECO:0007744|PDB:5MSP,
FT                   ECO:0007744|PDB:5MSR, ECO:0007744|PDB:5MSV"
FT   NP_BIND         868..869
FT                   /note="NADP"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_02247,
FT                   ECO:0000269|PubMed:28719588, ECO:0007744|PDB:5MSP,
FT                   ECO:0007744|PDB:5MSR, ECO:0007744|PDB:5MSV"
FT   NP_BIND         894..896
FT                   /note="NADP"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_02247,
FT                   ECO:0000269|PubMed:28719588, ECO:0007744|PDB:5MSP,
FT                   ECO:0007744|PDB:5MSR, ECO:0007744|PDB:5MSV"
FT   BINDING         315
FT                   /note="AMP"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_02247,
FT                   ECO:0000269|PubMed:28719588, ECO:0007744|PDB:5MST"
FT   BINDING         408
FT                   /note="AMP"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_02247,
FT                   ECO:0000269|PubMed:28719588, ECO:0007744|PDB:5MSS,
FT                   ECO:0007744|PDB:5MST, ECO:0007744|PDB:5MSW"
FT   BINDING         434
FT                   /note="AMP"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_02247,
FT                   ECO:0000269|PubMed:28719588, ECO:0007744|PDB:5MSS,
FT                   ECO:0007744|PDB:5MST, ECO:0007744|PDB:5MSW"
FT   BINDING         507
FT                   /note="AMP"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_02247,
FT                   ECO:0000269|PubMed:28719588, ECO:0007744|PDB:5MSS,
FT                   ECO:0007744|PDB:5MST, ECO:0007744|PDB:5MSW"
FT   BINDING         528
FT                   /note="AMP"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_02247,
FT                   ECO:0000269|PubMed:28719588, ECO:0007744|PDB:5MSS"
FT   BINDING         629
FT                   /note="AMP"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_02247,
FT                   ECO:0000269|PubMed:28719588, ECO:0007744|PDB:5MST,
FT                   ECO:0007744|PDB:5MSW"
FT   BINDING         828
FT                   /note="NADP"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_02247,
FT                   ECO:0000269|PubMed:28719588, ECO:0007744|PDB:5MSP,
FT                   ECO:0007744|PDB:5MSR, ECO:0007744|PDB:5MSV"
FT   BINDING         838
FT                   /note="NADP"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_02247,
FT                   ECO:0000269|PubMed:28719588, ECO:0007744|PDB:5MSP,
FT                   ECO:0007744|PDB:5MSR, ECO:0007744|PDB:5MSV"
FT   BINDING         934
FT                   /note="NADP; via carbonyl oxygen"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_02247,
FT                   ECO:0000269|PubMed:28719588, ECO:0007744|PDB:5MSP,
FT                   ECO:0007744|PDB:5MSR, ECO:0007744|PDB:5MSV"
FT   BINDING         970
FT                   /note="NADP"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_02247,
FT                   ECO:0000269|PubMed:28719588, ECO:0007744|PDB:5MSP,
FT                   ECO:0007744|PDB:5MSR, ECO:0007744|PDB:5MSV"
FT   BINDING         974
FT                   /note="NADP"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_02247,
FT                   ECO:0000269|PubMed:28719588, ECO:0007744|PDB:5MSR,
FT                   ECO:0007744|PDB:5MSV"
FT   BINDING         997
FT                   /note="NADP"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_02247,
FT                   ECO:0000269|PubMed:28719588, ECO:0007744|PDB:5MSP,
FT                   ECO:0007744|PDB:5MSR, ECO:0007744|PDB:5MSV"
FT   MOD_RES         702
FT                   /note="O-(pantetheine 4'-phosphoryl)serine"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_02247,
FT                   ECO:0000269|PubMed:28719588, ECO:0007744|PDB:5MSV"
FT   MUTAGEN         900
FT                   /note="H->P,N: Loss of activity."
FT                   /evidence="ECO:0000269|PubMed:28719588"
FT   MUTAGEN         966
FT                   /note="Y->P: Loss of activity."
FT                   /evidence="ECO:0000269|PubMed:28719588"
FT   MUTAGEN         998
FT                   /note="D->G: Does not affect benzoic acid reduction rates
FT                   but leads to alcohol production. Displays modest
FT                   benzaldehyde reductase activity."
FT                   /evidence="ECO:0000269|PubMed:28719588"
FT   MUTAGEN         1015
FT                   /note="Q->P: Loss of activity."
FT                   /evidence="ECO:0000269|PubMed:28719588"
FT   MUTAGEN         1018
FT                   /note="R->A: Loss of activity."
FT                   /evidence="ECO:0000269|PubMed:28719588"
FT   MUTAGEN         1131
FT                   /note="L->Y: Loss of activity."
FT                   /evidence="ECO:0000269|PubMed:28719588"
SQ   SEQUENCE   1188 AA;  128228 MW;  6E86BB01FEAB63D8 CRC64;
     MTESQSYETR QARPAGQSLA ERVARLVAID PQAAAAVPDK AVAERATQQG LRLAQRIEAF
     LSGYGDRPAL AQRAFEITKD PITGRAVATL LPKFETVSYR ELLERSHAIA SELANHAEAP
     VKAGEFIATI GFTSTDYTSL DIAGVLLGLT SVPLQTGATT DTLKAIAEET APAVFGASVE
     HLDNAVTTAL ATPSVRRLLV FDYRQGVDED REAVEAARSR LAEAGSAVLV DTLDEVIARG
     RALPRVALPP ATDAGDDSLS LLIYTSGSTG TPKGAMYPER NVAQFWGGIW HNAFDDGDSA
     PDVPDIMVNF MPLSHVAGRI GLMGTLSSGG TTYFIAKSDL STFFEDYSLA RPTKLFFVPR
     ICEMIYQHYQ SELDRIGAAD GSPQAEAIKT ELREKLLGGR VLTAGSGSAP MSPELTAFIE
     SVLQVHLVDG YGSTEAGPVW RDRKLVKPPV TEHKLIDVPE LGYFSTDSPY PRGELAIKTQ
     TILPGYYKRP ETTAEVFDED GFYLTGDVVA EVAPEEFVYV DRRKNVLKLS QGEFVALSKL
     EAAYGTSPLV RQISVYGSSQ RSYLLAVVVP TPEALAKYGD GEAVKSALGD SLQKIAREEG
     LQSYEVPRDF IIETDPFTIE NGILSDAGKT LRPKVKARYG ERLEALYAQL AETQAGELRS
     IRVGAGERPV IETVQRAAAA LLGASAAEVD PEAHFSDLGG DSLSALTYSN FLHEIFQVEV
     PVSVIVSAAN NLRSVAAHIE KERSSGSDRP TFASVHGAGA TTIRASDLKL EKFLDAQTLA
     AAPSLPRPAS EVRTVLLTGS NGWLGRFLAL AWLERLVPQG GKVVVIVRGK DDKAAKARLD
     SVFESGDPAL LAHYEDLADK GLEVLAGDFS DADLGLRKAD WDRLADEVDL IVHSGALVNH
     VLPYSQLFGP NVVGTAEVAK LALTKRLKPV TYLSTVAVAV GVEPSAFEED GDIRDVSAVR
     SIDEGYANGY GNSKWAGEVL LREAYEHAGL PVRVFRSDMI LAHRKYTGQL NVPDQFTRLI
     LSLLATGIAP KSFYQLDATG GRQRAHYDGI PVDFTAEAIT TLGLAGSDGY HSFDVFNPHH
     DGVGLDEFVD WLVEAGHPIS RVDDYAEWLS RFETSLRGLP EAQRQHSVLP LLHAFAQPAP
     AIDGSPFQTK NFQSSVQEAK VGAEHDIPHL DKALIVKYAE DIKQLGLL
//