PNAE_RAUSE
ID PNAE_RAUSE Reviewed; 264 AA.
AC Q9SE93;
DT 19-JUL-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 80.
DE RecName: Full=Polyneuridine-aldehyde esterase {ECO:0000305};
DE EC=3.1.1.78 {ECO:0000269|PubMed:10691977, ECO:0000269|PubMed:12071952};
DE AltName: Full=Polyneuridine aldehyde esterase {ECO:0000303|PubMed:10691977};
DE Flags: Precursor;
GN Name=PNAE {ECO:0000303|PubMed:10691977};
OS Rauvolfia serpentina (Serpentine wood) (Ophioxylon serpentinum).
OC Eukaryota; Viridiplantae; Streptophyta; Embryophyta; Tracheophyta;
OC Spermatophyta; Magnoliopsida; eudicotyledons; Gunneridae; Pentapetalae;
OC asterids; lamiids; Gentianales; Apocynaceae; Rauvolfioideae; Vinceae;
OC Rauvolfiinae; Rauvolfia.
OX NCBI_TaxID=4060;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], CATALYTIC ACTIVITY, PROTEIN SEQUENCE OF 7-23;
RP 104-149; 208-217 AND 226-235, AND FUNCTION.
RX PubMed=10691977; DOI=10.1046/j.1432-1327.2000.01136.x;
RA Dogru E., Warzecha H., Seibel F., Haebel S., Lottspeich F., Stoeckigt J.;
RT "The gene encoding polyneuridine aldehyde esterase of monoterpenoid indole
RT alkaloid biosynthesis in plants is an ortholog of the a/b hydrolase super
RT family.";
RL Eur. J. Biochem. 267:1397-1406(2000).
RN [2]
RP HOMODIMERIZATION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, ACTIVE SITES,
RP BIOPHYSICOCHEMICAL PROPERTIES, AND MUTAGENESIS OF HIS-17; CYS-20; HIS-86;
RP SER-87; CYS-132; GLY-152; CYS-170; CYS-213; ASP-216; HIS-244 AND CYS-257.
RX PubMed=12071952; DOI=10.1046/j.1432-1033.2002.02956.x;
RA Mattern-Dogru E., Ma X., Hartmann J., Decker H., Stoeckigt J.;
RT "Potential active-site residues in polyneuridine aldehyde esterase, a
RT central enzyme of indole alkaloid biosynthesis, by modelling and site-
RT directed mutagenesis.";
RL Eur. J. Biochem. 269:2889-2896(2002).
RN [3]
RP X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) IN COMPLEX WITH 16-EPIVELLOSIMINE.
RX PubMed=19496101; DOI=10.1002/anie.200900150;
RA Yang L., Hill M., Wang M., Panjikar S., Stockigt J.;
RT "Structural basis and enzymatic mechanism of the biosynthesis of C9- from
RT C10-monoterpenoid indole alkaloids.";
RL Angew. Chem. Int. Ed. Engl. 48:5211-5213(2009).
CC -!- FUNCTION: Catalyzes the hydrolysis of polyneuridine aldehyde into epi-
CC vellosimine, which is the immediate precursor for the synthesis of
CC ajmaline. {ECO:0000269|PubMed:10691977}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + polyneuridine aldehyde = 16-epivellosimine + CO2 +
CC methanol; Xref=Rhea:RHEA:17501, ChEBI:CHEBI:15377, ChEBI:CHEBI:16425,
CC ChEBI:CHEBI:16526, ChEBI:CHEBI:16829, ChEBI:CHEBI:17790; EC=3.1.1.78;
CC Evidence={ECO:0000269|PubMed:10691977, ECO:0000269|PubMed:12071952};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17502;
CC Evidence={ECO:0000269|PubMed:10691977, ECO:0000269|PubMed:12071952};
CC -!- ACTIVITY REGULATION: Inhibited by DEPC and HgCl(2).
CC {ECO:0000269|PubMed:12071952}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=36 uM for polyneuridine aldehyde {ECO:0000269|PubMed:12071952};
CC -!- PATHWAY: Alkaloid biosynthesis; ajmaline biosynthesis. {ECO:0000305}.
CC -!- SUBUNIT: Homodimer; homodimerizes in aqueous solutions at pH 7.0.
CC {ECO:0000269|PubMed:12071952}.
CC -!- MISCELLANEOUS: Ajmaline is an anti-arrhythmic alkaloid commercially
CC used as an efficient drug for the treatment of arrhythmic heart
CC disorder. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the AB hydrolase superfamily. {ECO:0000305}.
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DR EMBL; AF178576; AAF22288.1; -; mRNA.
DR PDB; 2WFL; X-ray; 2.10 A; A/B=1-264.
DR PDB; 2WFM; X-ray; 2.20 A; A/B/C/D/E=1-264.
DR PDB; 3GZJ; X-ray; 2.19 A; A/B/C/D/E=7-264.
DR PDBsum; 2WFL; -.
DR PDBsum; 2WFM; -.
DR PDBsum; 3GZJ; -.
DR AlphaFoldDB; Q9SE93; -.
DR SMR; Q9SE93; -.
DR ESTHER; rause-pnae; Hydroxynitrile_lyase.
DR KEGG; ag:AAF22288; -.
DR BioCyc; MetaCyc:MON-7725; -.
DR BRENDA; 3.1.1.78; 5309.
DR UniPathway; UPA00310; -.
DR EvolutionaryTrace; Q9SE93; -.
DR GO; GO:0050529; F:polyneuridine-aldehyde esterase activity; IDA:UniProtKB.
DR GO; GO:0035834; P:indole alkaloid metabolic process; IDA:UniProtKB.
DR Gene3D; 3.40.50.1820; -; 1.
DR InterPro; IPR029058; AB_hydrolase.
DR InterPro; IPR000073; AB_hydrolase_1.
DR InterPro; IPR045889; MES/HNL.
DR PANTHER; PTHR10992; PTHR10992; 1.
DR Pfam; PF12697; Abhydrolase_6; 1.
DR SUPFAM; SSF53474; SSF53474; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alkaloid metabolism; Direct protein sequencing; Hydrolase;
KW Serine esterase.
FT PROPEP 1..6
FT /evidence="ECO:0000269|PubMed:10691977"
FT /id="PRO_0000022077"
FT CHAIN 7..264
FT /note="Polyneuridine-aldehyde esterase"
FT /id="PRO_0000022078"
FT DOMAIN 12..122
FT /note="AB hydrolase-1"
FT /evidence="ECO:0000255"
FT ACT_SITE 87
FT /evidence="ECO:0000269|PubMed:12071952"
FT ACT_SITE 216
FT /evidence="ECO:0000269|PubMed:12071952"
FT ACT_SITE 244
FT /evidence="ECO:0000269|PubMed:12071952"
FT BINDING 87
FT /ligand="16-epivellosimine"
FT /ligand_id="ChEBI:CHEBI:16425"
FT /note="covalent"
FT /evidence="ECO:0000269|PubMed:19496101,
FT ECO:0007744|PDB:3GZJ"
FT MUTAGEN 17
FT /note="H->A: No effect."
FT /evidence="ECO:0000269|PubMed:12071952"
FT MUTAGEN 20
FT /note="C->A: Loss of function."
FT /evidence="ECO:0000269|PubMed:12071952"
FT MUTAGEN 86
FT /note="H->A: Loss of function."
FT /evidence="ECO:0000269|PubMed:12071952"
FT MUTAGEN 87
FT /note="S->A: Loss of function."
FT /evidence="ECO:0000269|PubMed:12071952"
FT MUTAGEN 132
FT /note="C->A: No effect."
FT /evidence="ECO:0000269|PubMed:12071952"
FT MUTAGEN 152
FT /note="G->Q: No effect; when associated with S-213."
FT /evidence="ECO:0000269|PubMed:12071952"
FT MUTAGEN 170
FT /note="C->A: No effect."
FT /evidence="ECO:0000269|PubMed:12071952"
FT MUTAGEN 213
FT /note="C->S: No effect; when associated with Q-152."
FT /evidence="ECO:0000269|PubMed:12071952"
FT MUTAGEN 216
FT /note="D->A: Loss of function."
FT /evidence="ECO:0000269|PubMed:12071952"
FT MUTAGEN 244
FT /note="H->A: Loss of function."
FT /evidence="ECO:0000269|PubMed:12071952"
FT MUTAGEN 257
FT /note="C->A: No effect."
FT /evidence="ECO:0000269|PubMed:12071952"
FT STRAND 12..16
FT /evidence="ECO:0007829|PDB:2WFL"
FT HELIX 23..26
FT /evidence="ECO:0007829|PDB:2WFL"
FT HELIX 29..35
FT /evidence="ECO:0007829|PDB:2WFL"
FT STRAND 39..43
FT /evidence="ECO:0007829|PDB:2WFL"
FT HELIX 55..57
FT /evidence="ECO:0007829|PDB:2WFL"
FT HELIX 61..74
FT /evidence="ECO:0007829|PDB:2WFL"
FT STRAND 81..86
FT /evidence="ECO:0007829|PDB:2WFL"
FT HELIX 89..99
FT /evidence="ECO:0007829|PDB:2WFL"
FT HELIX 101..103
FT /evidence="ECO:0007829|PDB:2WFL"
FT STRAND 104..112
FT /evidence="ECO:0007829|PDB:2WFL"
FT HELIX 123..131
FT /evidence="ECO:0007829|PDB:2WFL"
FT TURN 134..139
FT /evidence="ECO:0007829|PDB:2WFL"
FT STRAND 141..146
FT /evidence="ECO:0007829|PDB:2WFL"
FT STRAND 152..156
FT /evidence="ECO:0007829|PDB:2WFL"
FT HELIX 159..165
FT /evidence="ECO:0007829|PDB:2WFL"
FT HELIX 172..181
FT /evidence="ECO:0007829|PDB:2WFL"
FT HELIX 189..192
FT /evidence="ECO:0007829|PDB:2WFL"
FT TURN 200..202
FT /evidence="ECO:0007829|PDB:2WFL"
FT HELIX 203..205
FT /evidence="ECO:0007829|PDB:2WFL"
FT STRAND 208..213
FT /evidence="ECO:0007829|PDB:2WFL"
FT STRAND 217..219
FT /evidence="ECO:0007829|PDB:2WFL"
FT HELIX 221..231
FT /evidence="ECO:0007829|PDB:2WFL"
FT STRAND 234..239
FT /evidence="ECO:0007829|PDB:2WFL"
FT HELIX 246..249
FT /evidence="ECO:0007829|PDB:2WFL"
FT HELIX 251..262
FT /evidence="ECO:0007829|PDB:2WFL"
SQ SEQUENCE 264 AA; 29655 MW; 3836517100C6E2DD CRC64;
MHSAANAKQQ KHFVLVHGGC LGAWIWYKLK PLLESAGHKV TAVDLSAAGI NPRRLDEIHT
FRDYSEPLME VMASIPPDEK VVLLGHSFGG MSLGLAMETY PEKISVAVFM SAMMPDPNHS
LTYPFEKYNE KCPADMMLDS QFSTYGNPEN PGMSMILGPQ FMALKMFQNC SVEDLELAKM
LTRPGSLFFQ DLAKAKKFST ERYGSVKRAY IFCNEDKSFP VEFQKWFVES VGADKVKEIK
EADHMGMLSQ PREVCKCLLD ISDS
