SARED_ESCCA
ID SARED_ESCCA Reviewed; 273 AA.
AC D5JWB3;
DT 04-MAR-2015, integrated into UniProtKB/Swiss-Prot.
DT 15-JUN-2010, sequence version 1.
DT 03-AUG-2022, entry version 38.
DE RecName: Full=Sanguinarine reductase {ECO:0000303|PubMed:17080644};
DE EC=1.3.1.107 {ECO:0000305};
GN Name=SARED1 {ECO:0000303|PubMed:17080644};
OS Eschscholzia californica (California poppy).
OC Eukaryota; Viridiplantae; Streptophyta; Embryophyta; Tracheophyta;
OC Spermatophyta; Magnoliopsida; Ranunculales; Papaveraceae;
OC Eschscholzioideae; Eschscholzia.
OX NCBI_TaxID=3467 {ECO:0000312|EMBL:ADE41047.1};
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], PROTEIN SEQUENCE OF 34-46; 49-92;
RP 147-242 AND 264-273, 3D-STRUCTURE MODELING, FUNCTION, CATALYTIC ACTIVITY,
RP ACTIVITY REGULATION, SUBUNIT, AND MUTAGENESIS OF 102-SER--MET-114; SER-153;
RP CYS-157; ASP-158; HIS-161; PHE-162 AND MET-166.
RX PubMed=20378534; DOI=10.1074/jbc.m109.088989;
RA Vogel M., Lawson M., Sippl W., Conrad U., Roos W.;
RT "Structure and mechanism of sanguinarine reductase, an enzyme of alkaloid
RT detoxification.";
RL J. Biol. Chem. 285:18397-18406(2010).
RN [2]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND SUBSTRATE
RP SPECIFICITY.
RX PubMed=17080644; DOI=10.1111/j.1365-3040.2005.01421.x;
RA Weiss D., Baumert A., Vogel M., Roos W.;
RT "Sanguinarine reductase, a key enzyme of benzophenanthridine
RT detoxification.";
RL Plant Cell Environ. 29:291-302(2006).
CC -!- FUNCTION: Catalyzes the reduction of benzophenanthridines,
CC preferentially sanguinarine, to the corresponding dihydroalkaloids.
CC Involved in detoxifying the phytoalexins produced by plant itself. The
CC sanguinarine produced by intact cells upon elicitation, after excretion
CC and binding to cell wall elements, is rapidly reabsorbed and reduced to
CC the less toxic dihydrosanguinarine. Can work with both NAD(P) or NAD as
CC a hydrogen donor, but at low concentrations, the reaction velocity with
CC NAD(P)H is threefold higher than with NADH. However, chelerythrine
CC shows maximum conversion rates with NADH. The substrate preference is
CC sanguinarine > chelerythrine > chelirubine, macarpine or 10-OH-
CC chelerythrine. No activity with berberine or phenanthridine cations.
CC {ECO:0000269|PubMed:17080644, ECO:0000269|PubMed:20378534}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=dihydrosanguinarine + NADP(+) = NADPH + sanguinarine;
CC Xref=Rhea:RHEA:41656, ChEBI:CHEBI:17183, ChEBI:CHEBI:17209,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.3.1.107;
CC Evidence={ECO:0000269|PubMed:17080644, ECO:0000269|PubMed:20378534};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=dihydrosanguinarine + NAD(+) = NADH + sanguinarine;
CC Xref=Rhea:RHEA:41660, ChEBI:CHEBI:17183, ChEBI:CHEBI:17209,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.3.1.107;
CC Evidence={ECO:0000269|PubMed:17080644, ECO:0000269|PubMed:20378534};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=dihydrochelirubine + NAD(+) = chelirubine + NADH;
CC Xref=Rhea:RHEA:41664, ChEBI:CHEBI:17031, ChEBI:CHEBI:17789,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.3.1.107;
CC Evidence={ECO:0000269|PubMed:17080644, ECO:0000269|PubMed:20378534};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=dihydrochelirubine + NADP(+) = chelirubine + NADPH;
CC Xref=Rhea:RHEA:41668, ChEBI:CHEBI:17031, ChEBI:CHEBI:17789,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.3.1.107;
CC Evidence={ECO:0000269|PubMed:17080644, ECO:0000269|PubMed:20378534};
CC -!- ACTIVITY REGULATION: Inhibited by iodoacetamide and irreversibly by its
CC product, dihydrosanguinarine. {ECO:0000269|PubMed:20378534}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=9.5 uM for sanguinarine (in the presence of 40 uM NADH)
CC {ECO:0000269|PubMed:17080644};
CC pH dependence:
CC Optimum pH is 6.5-7.5. {ECO:0000269|PubMed:17080644};
CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:20378534}.
CC -!- SIMILARITY: Belongs to the NAD(P)-dependent epimerase/dehydratase
CC family. {ECO:0000305}.
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DR EMBL; GU338458; ADE41047.1; -; Genomic_DNA.
DR AlphaFoldDB; D5JWB3; -.
DR SMR; D5JWB3; -.
DR KEGG; ag:ADE41047; -.
DR BioCyc; MetaCyc:MON-13854; -.
DR BRENDA; 1.3.1.107; 2173.
DR GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR GO; GO:0009636; P:response to toxic substance; IEA:UniProtKB-KW.
DR InterPro; IPR016040; NAD(P)-bd_dom.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR044163; SARED1-like.
DR PANTHER; PTHR14194; PTHR14194; 1.
DR Pfam; PF13460; NAD_binding_10; 1.
DR SUPFAM; SSF51735; SSF51735; 1.
PE 1: Evidence at protein level;
KW Detoxification; Direct protein sequencing; NAD; NADP; Oxidoreductase.
FT CHAIN 1..273
FT /note="Sanguinarine reductase"
FT /id="PRO_0000432076"
FT ACT_SITE 153
FT /note="Proton donor"
FT /evidence="ECO:0000305|PubMed:20378534"
FT BINDING 157..161
FT /ligand="substrate"
FT /evidence="ECO:0000305|PubMed:20378534"
FT BINDING 175
FT /ligand="substrate"
FT /evidence="ECO:0000305|PubMed:20378534"
FT MUTAGEN 102..114
FT /note="Missing: Loss of catalytic activity."
FT /evidence="ECO:0000269|PubMed:20378534"
FT MUTAGEN 153
FT /note="S->A: Loss of catalytic activity."
FT /evidence="ECO:0000269|PubMed:20378534"
FT MUTAGEN 157
FT /note="C->A: Strongly decreased catalytic activity."
FT /evidence="ECO:0000269|PubMed:20378534"
FT MUTAGEN 158
FT /note="D->N: Slightly decreased catalytic activity."
FT /evidence="ECO:0000269|PubMed:20378534"
FT MUTAGEN 161
FT /note="H->A: Strongly decreased catalytic activity."
FT /evidence="ECO:0000269|PubMed:20378534"
FT MUTAGEN 162
FT /note="F->P: Slightly decreased catalytic activity."
FT /evidence="ECO:0000269|PubMed:20378534"
FT MUTAGEN 166
FT /note="M->L: No effect on catalytic activity."
FT /evidence="ECO:0000269|PubMed:20378534"
SQ SEQUENCE 273 AA; 29520 MW; F8078484C3B9BCE9 CRC64;
MADSSKKLTV LLSGASGLTG SLAFKKLKER SDKFEVRGLV RSEASKQKLG GGDEIFIGDI
SDPKTLEPAM EGIDALIILT SAIPRMKPTE EFTAEMISGG RSEDVIDASF SGPMPEFYYD
EGQYPEQVDW IGQKNQIDTA KKMGVKHIVL VGSMGGCDPD HFLNHMGNGN ILIWKRKAEQ
YLADSGVPYT IIRAGGLDNK AGGVRELLVA KDDVLLPTEN GFIARADVAE ACVQALEIEE
VKNKAFDLGS KPEGVGEATK DFKALFSQVT TPF
