OAT_PLAF7
ID OAT_PLAF7 Reviewed; 414 AA.
AC Q6LFH8; Q9GQI3;
DT 02-MAY-2006, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 25-MAY-2022, entry version 115.
DE RecName: Full=Ornithine aminotransferase {ECO:0000303|PubMed:11704268};
DE Short=PfOAT {ECO:0000303|PubMed:20673832};
DE EC=2.6.1.13 {ECO:0000269|PubMed:11704268, ECO:0000269|PubMed:20673832};
DE AltName: Full=Ornithine--oxo-acid aminotransferase {ECO:0000305};
GN Name=OAT {ECO:0000303|PubMed:11704268}; ORFNames=PF3D7_0608800, PFF0435w;
OS Plasmodium falciparum (isolate 3D7).
OC Eukaryota; Sar; Alveolata; Apicomplexa; Aconoidasida; Haemosporida;
OC Plasmodiidae; Plasmodium; Plasmodium (Laverania).
OX NCBI_TaxID=36329;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, CATALYTIC ACTIVITY,
RP BIOPHYSICOCHEMICAL PROPERTIES, AND PATHWAY.
RX PubMed=11704268; DOI=10.1016/s0166-6851(01)00357-7;
RA Gafan C., Wilson J., Berger L.C., Berger B.J.;
RT "Characterization of the ornithine aminotransferase from Plasmodium
RT falciparum.";
RL Mol. Biochem. Parasitol. 118:1-10(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=3D7;
RX PubMed=12368864; DOI=10.1038/nature01097;
RA Gardner M.J., Hall N., Fung E., White O., Berriman M., Hyman R.W.,
RA Carlton J.M., Pain A., Nelson K.E., Bowman S., Paulsen I.T., James K.D.,
RA Eisen J.A., Rutherford K.M., Salzberg S.L., Craig A., Kyes S., Chan M.-S.,
RA Nene V., Shallom S.J., Suh B., Peterson J., Angiuoli S., Pertea M.,
RA Allen J., Selengut J., Haft D., Mather M.W., Vaidya A.B., Martin D.M.A.,
RA Fairlamb A.H., Fraunholz M.J., Roos D.S., Ralph S.A., McFadden G.I.,
RA Cummings L.M., Subramanian G.M., Mungall C., Venter J.C., Carucci D.J.,
RA Hoffman S.L., Newbold C., Davis R.W., Fraser C.M., Barrell B.G.;
RT "Genome sequence of the human malaria parasite Plasmodium falciparum.";
RL Nature 419:498-511(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=3D7;
RX PubMed=12368867; DOI=10.1038/nature01095;
RA Hall N., Pain A., Berriman M., Churcher C.M., Harris B., Harris D.,
RA Mungall K.L., Bowman S., Atkin R., Baker S., Barron A., Brooks K.,
RA Buckee C.O., Burrows C., Cherevach I., Chillingworth C., Chillingworth T.,
RA Christodoulou Z., Clark L., Clark R., Corton C., Cronin A., Davies R.M.,
RA Davis P., Dear P., Dearden F., Doggett J., Feltwell T., Goble A.,
RA Goodhead I., Gwilliam R., Hamlin N., Hance Z., Harper D., Hauser H.,
RA Hornsby T., Holroyd S., Horrocks P., Humphray S., Jagels K., James K.D.,
RA Johnson D., Kerhornou A., Knights A., Konfortov B., Kyes S., Larke N.,
RA Lawson D., Lennard N., Line A., Maddison M., Mclean J., Mooney P.,
RA Moule S., Murphy L., Oliver K., Ormond D., Price C., Quail M.A.,
RA Rabbinowitsch E., Rajandream M.A., Rutter S., Rutherford K.M., Sanders M.,
RA Simmonds M., Seeger K., Sharp S., Smith R., Squares R., Squares S.,
RA Stevens K., Taylor K., Tivey A., Unwin L., Whitehead S., Woodward J.R.,
RA Sulston J.E., Craig A., Newbold C., Barrell B.G.;
RT "Sequence of Plasmodium falciparum chromosomes 1, 3-9 and 13.";
RL Nature 419:527-531(2002).
RN [4] {ECO:0007744|PDB:3LG0, ECO:0007744|PDB:3NTJ}
RP X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS), FUNCTION, CATALYTIC ACTIVITY,
RP ACTIVITY REGULATION, BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT, DISULFIDE
RP BOND, AND MUTAGENESIS OF CYS-154; CYS-163; CYS-316; CYS-350 AND CYS-390.
RX PubMed=20673832; DOI=10.1016/j.jmb.2010.07.039;
RA Jortzik E., Fritz-Wolf K., Sturm N., Hipp M., Rahlfs S., Becker K.;
RT "Redox regulation of Plasmodium falciparum ornithine delta-
RT aminotransferase.";
RL J. Mol. Biol. 402:445-459(2010).
CC -!- FUNCTION: The enzyme has a very narrow substrate specificity and can
CC only catalyze the transamination of alpha-ketoglutarate with ornithine
CC or N-acetylornithine and, to a lesser extent, of glutamate-5-
CC semialdehyde with glutamate and alanine. {ECO:0000269|PubMed:11704268,
CC ECO:0000269|PubMed:20673832}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 2-oxocarboxylate + L-ornithine = an L-alpha-amino acid + L-
CC glutamate 5-semialdehyde; Xref=Rhea:RHEA:13877, ChEBI:CHEBI:35179,
CC ChEBI:CHEBI:46911, ChEBI:CHEBI:58066, ChEBI:CHEBI:59869; EC=2.6.1.13;
CC Evidence={ECO:0000269|PubMed:11704268};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-oxoglutarate + L-ornithine = L-glutamate + L-glutamate 5-
CC semialdehyde; Xref=Rhea:RHEA:25160, ChEBI:CHEBI:16810,
CC ChEBI:CHEBI:29985, ChEBI:CHEBI:46911, ChEBI:CHEBI:58066; EC=2.6.1.13;
CC Evidence={ECO:0000269|PubMed:11704268, ECO:0000269|PubMed:20673832};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:25161;
CC Evidence={ECO:0000269|PubMed:11704268, ECO:0000269|PubMed:20673832};
CC -!- COFACTOR:
CC Name=pyridoxal 5'-phosphate; Xref=ChEBI:CHEBI:597326;
CC Evidence={ECO:0000250|UniProtKB:P04181};
CC -!- ACTIVITY REGULATION: Unlike for mammalian OATs, activity is increased
CC by TRX1-mediated reduction of the disulfide bond between Cys-154 and
CC Cys-163 (PubMed:20673832). Binding to TRX1 may also induce
CC conformational changes that facilitate substrate binding
CC (PubMed:20673832). {ECO:0000269|PubMed:20673832}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=3.95 mM for ornithine (at 37 degrees Celsius, pH 7.4 and with 2-
CC oxoglutarate as cosubstrate) {ECO:0000269|PubMed:11704268};
CC KM=1.6 mM for ornithine (at 37 degrees Celsius, pH 7.4 and with 2-
CC oxoglutarate as cosubstrate) {ECO:0000269|PubMed:20673832};
CC KM=0.9 mM for ornithine (at 37 degrees Celsius, pH 7.4, with 2-
CC oxoglutarate as cosubstrate and in presence of TRX1/thioredoxin)
CC {ECO:0000269|PubMed:20673832};
CC KM=1.53 mM for N-acetylornithine (at 37 degrees Celsius, pH 7.4 and
CC with 2-oxoglutarate as cosubstrate) {ECO:0000269|PubMed:11704268};
CC KM=0.65 mM for 2-oxoglutarate (at 37 degrees Celsius, pH 7.4 and with
CC ornithine as cosubstrate) {ECO:0000269|PubMed:11704268};
CC KM=0.9 mM for 2-oxoglutarate (at 37 degrees Celsius, pH 7.4 and with
CC ornithine as cosubstrate) {ECO:0000269|PubMed:11704268};
CC KM=0.3 mM for 2-oxoglutarate (at 37 degrees Celsius, pH 7.4, with
CC ornithine as cosubstrate and in presence of TRX1/thioredoxin)
CC {ECO:0000269|PubMed:11704268};
CC Vmax=56.12 nmol/min/mg enzyme towards ornithine (at 37 degrees
CC Celsius, pH 7.4 and with 2-oxoglutarate as cosubstrate)
CC {ECO:0000269|PubMed:11704268};
CC Vmax=18.56 nmol/min/mg enzyme towards N-acetylornithine (at 37
CC degrees Celsius, pH 7.4 and with 2-oxoglutarate as cosubstrate)
CC {ECO:0000269|PubMed:11704268};
CC Vmax=30.28 nmol/min/mg enzyme towards 2-oxoglutarate (at 37 degrees
CC Celsius, pH 7.4 and with ornithine as cosubstrate)
CC {ECO:0000269|PubMed:11704268};
CC -!- PATHWAY: Amino-acid biosynthesis; L-proline biosynthesis; L-glutamate
CC 5-semialdehyde from L-ornithine: step 1/1.
CC {ECO:0000269|PubMed:11704268}.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:20673832}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000305}.
CC -!- PTM: The disulfide bond between Cys-154 and Cys-163 is reduced by TRX1
CC which increases OAT catalytic activity. {ECO:0000269|PubMed:20673832}.
CC -!- SIMILARITY: Belongs to the class-III pyridoxal-phosphate-dependent
CC aminotransferase family. {ECO:0000305}.
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DR EMBL; AF249587; AAG44560.1; -; Genomic_DNA.
DR EMBL; AL844505; CAG25330.1; -; Genomic_DNA.
DR RefSeq; XP_966078.1; XM_960985.1.
DR PDB; 3LG0; X-ray; 2.30 A; A/B/C/D=1-414.
DR PDB; 3NTJ; X-ray; 3.00 A; A/B/C/D=1-414.
DR PDBsum; 3LG0; -.
DR PDBsum; 3NTJ; -.
DR AlphaFoldDB; Q6LFH8; -.
DR SMR; Q6LFH8; -.
DR IntAct; Q6LFH8; 1.
DR MINT; Q6LFH8; -.
DR STRING; 5833.PFF0435w; -.
DR DrugBank; DB11638; Artenimol.
DR SwissPalm; Q6LFH8; -.
DR PRIDE; Q6LFH8; -.
DR EnsemblProtists; CAG25330; CAG25330; PF3D7_0608800.
DR GeneID; 3885911; -.
DR KEGG; pfa:PF3D7_0608800; -.
DR VEuPathDB; PlasmoDB:PF3D7_0608800; -.
DR HOGENOM; CLU_016922_10_3_1; -.
DR InParanoid; Q6LFH8; -.
DR OMA; DVFPRFA; -.
DR PhylomeDB; Q6LFH8; -.
DR BRENDA; 2.6.1.13; 4889.
DR Reactome; R-PFA-8964539; Glutamate and glutamine metabolism.
DR UniPathway; UPA00098; UER00358.
DR EvolutionaryTrace; Q6LFH8; -.
DR Proteomes; UP000001450; Chromosome 6.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0042802; F:identical protein binding; IBA:GO_Central.
DR GO; GO:0050155; F:ornithine(lysine) transaminase activity; IEA:UniProtKB-EC.
DR GO; GO:0004587; F:ornithine-oxo-acid transaminase activity; IDA:UniProtKB.
DR GO; GO:0030170; F:pyridoxal phosphate binding; IBA:GO_Central.
DR GO; GO:0019544; P:arginine catabolic process to glutamate; IBA:GO_Central.
DR GO; GO:0010121; P:arginine catabolic process to proline via ornithine; IBA:GO_Central.
DR GO; GO:0055129; P:L-proline biosynthetic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0006591; P:ornithine metabolic process; IDA:UniProtKB.
DR CDD; cd00610; OAT_like; 1.
DR Gene3D; 3.40.640.10; -; 1.
DR Gene3D; 3.90.1150.10; -; 1.
DR InterPro; IPR005814; Aminotrans_3.
DR InterPro; IPR010164; Orn_aminotrans.
DR InterPro; IPR015424; PyrdxlP-dep_Trfase.
DR InterPro; IPR015421; PyrdxlP-dep_Trfase_major.
DR InterPro; IPR015422; PyrdxlP-dep_Trfase_small.
DR PANTHER; PTHR11986:SF18; PTHR11986:SF18; 1.
DR Pfam; PF00202; Aminotran_3; 1.
DR PIRSF; PIRSF000521; Transaminase_4ab_Lys_Orn; 1.
DR SUPFAM; SSF53383; SSF53383; 1.
DR TIGRFAMs; TIGR01885; Orn_aminotrans; 1.
DR PROSITE; PS00600; AA_TRANSFER_CLASS_3; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Aminotransferase; Cytoplasm; Disulfide bond;
KW Pyridoxal phosphate; Reference proteome; Transferase.
FT CHAIN 1..414
FT /note="Ornithine aminotransferase"
FT /id="PRO_0000233395"
FT MOD_RES 262
FT /note="N6-(pyridoxal phosphate)lysine"
FT /evidence="ECO:0000250|UniProtKB:P04181"
FT DISULFID 154..163
FT /note="Reversible"
FT /evidence="ECO:0000269|PubMed:20673832"
FT MUTAGEN 154
FT /note="C->S: Severe reduction in catalytic activity. Does
FT not affect TRX1-mediated activation. Severe reduction in
FT catalytic activity and loss of TRX1-mediated activation;
FT when associated with S-163."
FT /evidence="ECO:0000269|PubMed:20673832"
FT MUTAGEN 163
FT /note="C->S: No effect on catalytic activity. Requires
FT higher concentrations of TRX1 for activation. Severe
FT reduction in catalytic activity and loss of TRX1-mediated
FT activation; when associated with S-154."
FT /evidence="ECO:0000269|PubMed:20673832"
FT MUTAGEN 316
FT /note="C->S: About 70% reduction in catalytic activity.
FT Does not affect TRX1-mediated activation."
FT /evidence="ECO:0000269|PubMed:20673832"
FT MUTAGEN 350
FT /note="C->S: About 70% reduction in catalytic activity.
FT Does not affect TRX1-mediated activation."
FT /evidence="ECO:0000269|PubMed:20673832"
FT MUTAGEN 390
FT /note="C->S: About 70% reduction in catalytic activity.
FT Does not affect TRX1-mediated activation."
FT /evidence="ECO:0000269|PubMed:20673832"
FT CONFLICT 153
FT /note="G -> S (in Ref. 1; AAG44560)"
FT /evidence="ECO:0000305"
FT CONFLICT 190
FT /note="Q -> H (in Ref. 1; AAG44560)"
FT /evidence="ECO:0000305"
FT CONFLICT 197..198
FT /note="FI -> LN (in Ref. 1; AAG44560)"
FT /evidence="ECO:0000305"
FT CONFLICT 206
FT /note="A -> V (in Ref. 1; AAG44560)"
FT /evidence="ECO:0000305"
FT CONFLICT 413
FT /note="N -> K (in Ref. 1; AAG44560)"
FT /evidence="ECO:0000305"
FT HELIX 10..20
FT /evidence="ECO:0007829|PDB:3NTJ"
FT STRAND 31..37
FT /evidence="ECO:0007829|PDB:3NTJ"
FT STRAND 39..42
FT /evidence="ECO:0007829|PDB:3NTJ"
FT STRAND 47..52
FT /evidence="ECO:0007829|PDB:3NTJ"
FT HELIX 53..56
FT /evidence="ECO:0007829|PDB:3NTJ"
FT TURN 57..60
FT /evidence="ECO:0007829|PDB:3NTJ"
FT HELIX 65..77
FT /evidence="ECO:0007829|PDB:3NTJ"
FT STRAND 85..87
FT /evidence="ECO:0007829|PDB:3NTJ"
FT HELIX 88..101
FT /evidence="ECO:0007829|PDB:3NTJ"
FT STRAND 104..111
FT /evidence="ECO:0007829|PDB:3NTJ"
FT HELIX 112..129
FT /evidence="ECO:0007829|PDB:3NTJ"
FT STRAND 139..143
FT /evidence="ECO:0007829|PDB:3NTJ"
FT STRAND 174..177
FT /evidence="ECO:0007829|PDB:3NTJ"
FT HELIX 182..189
FT /evidence="ECO:0007829|PDB:3NTJ"
FT STRAND 194..199
FT /evidence="ECO:0007829|PDB:3NTJ"
FT STRAND 201..203
FT /evidence="ECO:0007829|PDB:3NTJ"
FT TURN 204..207
FT /evidence="ECO:0007829|PDB:3NTJ"
FT HELIX 215..226
FT /evidence="ECO:0007829|PDB:3NTJ"
FT STRAND 229..233
FT /evidence="ECO:0007829|PDB:3NTJ"
FT TURN 235..242
FT /evidence="ECO:0007829|PDB:3NTJ"
FT STRAND 243..246
FT /evidence="ECO:0007829|PDB:3NTJ"
FT HELIX 247..251
FT /evidence="ECO:0007829|PDB:3NTJ"
FT STRAND 256..260
FT /evidence="ECO:0007829|PDB:3NTJ"
FT HELIX 262..265
FT /evidence="ECO:0007829|PDB:3NTJ"
FT STRAND 272..276
FT /evidence="ECO:0007829|PDB:3NTJ"
FT HELIX 278..281
FT /evidence="ECO:0007829|PDB:3NTJ"
FT TURN 292..295
FT /evidence="ECO:0007829|PDB:3NTJ"
FT HELIX 297..312
FT /evidence="ECO:0007829|PDB:3NTJ"
FT HELIX 315..333
FT /evidence="ECO:0007829|PDB:3NTJ"
FT TURN 334..336
FT /evidence="ECO:0007829|PDB:3NTJ"
FT STRAND 338..346
FT /evidence="ECO:0007829|PDB:3NTJ"
FT STRAND 349..354
FT /evidence="ECO:0007829|PDB:3NTJ"
FT TURN 356..358
FT /evidence="ECO:0007829|PDB:3NTJ"
FT HELIX 361..371
FT /evidence="ECO:0007829|PDB:3NTJ"
FT TURN 379..381
FT /evidence="ECO:0007829|PDB:3NTJ"
FT STRAND 382..385
FT /evidence="ECO:0007829|PDB:3NTJ"
FT HELIX 393..412
FT /evidence="ECO:0007829|PDB:3NTJ"
SQ SEQUENCE 414 AA; 46055 MW; EA2264D1FA264DBF CRC64;
MDFVKELKSS QDYMNNELTY GAHNYDPIPV VLKRGKGVFV YDIEDRRYYD FLSAYSSVNQ
GHCHPDILNA MINQAKKLTI CSRAFFSDSL GVCERYLTNL FGYDKVLMMN TGAEASETAY
KLCRKWGYEV KKIPENSAKI IVCNNNFSGR TLGCVSASTD KKCKNNFGPF VPNFLKVPYD
DLEALEKELQ DPNVCAFIVE PVQGEAGVIV PSDSYFPGVA SLCKKYNVLF VADEVQTGLG
RTGKLLCTHH YGVKPDVILL GKALSGGHYP ISAILANDDV MLVLKPGEHG STYGGNPLAA
AICVEALKVL INEKLCENAD KLGAPFLQNL KEQLKDSKVV REVRGKGLLC AIEFKNDLVN
VWDICLKFKE NGLITRSVHD KTVRLTPPLC ITKEQLDECT EIIVKTVKFF DDNL
