ID   ORNAT_PYRHO             Reviewed;         454 AA.
AC   O50131;
DT   13-SEP-2023, integrated into UniProtKB/Swiss-Prot.
DT   01-JUN-1998, sequence version 1.
DT   27-MAR-2024, entry version 132.
DE   RecName: Full=Ornithine aminotransferase {ECO:0000305};
DE            Short=Orn-AT {ECO:0000303|PubMed:35337912};
DE            EC=2.6.1.13 {ECO:0000269|PubMed:35337912};
DE   AltName: Full=Ornithine delta-aminotransferase {ECO:0000303|PubMed:35337912};
GN   OrderedLocusNames=PH1423 {ECO:0000312|EMBL:BAA30529.1};
OS   Pyrococcus horikoshii (strain ATCC 700860 / DSM 12428 / JCM 9974 / NBRC
OS   100139 / OT-3).
OC   Archaea; Euryarchaeota; Thermococci; Thermococcales; Thermococcaceae;
OC   Pyrococcus.
OX   NCBI_TaxID=70601;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 700860 / DSM 12428 / JCM 9974 / NBRC 100139 / OT-3;
RX   PubMed=9679194; DOI=10.1093/dnares/5.2.55;
RA   Kawarabayasi Y., Sawada M., Horikawa H., Haikawa Y., Hino Y., Yamamoto S.,
RA   Sekine M., Baba S., Kosugi H., Hosoyama A., Nagai Y., Sakai M., Ogura K.,
RA   Otsuka R., Nakazawa H., Takamiya M., Ohfuku Y., Funahashi T., Tanaka T.,
RA   Kudoh Y., Yamazaki J., Kushida N., Oguchi A., Aoki K., Yoshizawa T.,
RA   Nakamura Y., Robb F.T., Horikoshi K., Masuchi Y., Shizuya H., Kikuchi H.;
RT   "Complete sequence and gene organization of the genome of a hyper-
RT   thermophilic archaebacterium, Pyrococcus horikoshii OT3.";
RL   DNA Res. 5:55-76(1998).
RN   [2] {ECO:0007744|PDB:7VNO, ECO:0007744|PDB:7VNT, ECO:0007744|PDB:7VO1}
RP   X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) IN COMPLEXES WITH PYRIDOXAL
RP   PHOSPHATE; L-ORNITHINE AND REACTION INTERMEDIATE ANALOG PLP-L-GLU,
RP   FUNCTION, CATALYTIC ACTIVITY, COFACTOR, BIOPHYSICOCHEMICAL PROPERTIES,
RP   SUBUNIT, DOMAIN, AND MUTAGENESIS OF THR-92 AND ASP-93.
RX   PubMed=35337912; DOI=10.1016/j.ijbiomac.2022.03.114;
RA   Kawakami R., Ohshida T., Hayashi J., Yoneda K., Furumoto T., Ohshima T.,
RA   Sakuraba H.;
RT   "Crystal structure of a novel type of ornithine delta-aminotransferase from
RT   the hyperthermophilic archaeon Pyrococcus horikoshii.";
RL   Int. J. Biol. Macromol. 208:731-740(2022).
CC   -!- FUNCTION: Catalyzes the conversion of L-ornithine and 2-oxoglutarate to
CC       L-glutamate semialdehyde and L-glutamate (PubMed:35337912). L-ornithine
CC       is the best substrate, but the enzyme also shows good activity toward
CC       L-lysine, and low activity toward D-ornithine, D-lysine, 5-
CC       aminovalerate, 6-aminohexanoate and GABA (PubMed:35337912). The enzyme
CC       activity is specific for 2-oxoglutarate (PubMed:35337912).
CC       {ECO:0000269|PubMed:35337912}.
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:35337912};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=2-oxoglutarate + L-lysine = (S)-2-amino-6-oxohexanoate + L-
CC         glutamate; Xref=Rhea:RHEA:21200, ChEBI:CHEBI:16810,
CC         ChEBI:CHEBI:29985, ChEBI:CHEBI:32551, ChEBI:CHEBI:58321;
CC         Evidence={ECO:0000269|PubMed:35337912};
CC   -!- COFACTOR:
CC       Name=pyridoxal 5'-phosphate; Xref=ChEBI:CHEBI:597326;
CC         Evidence={ECO:0000269|PubMed:35337912};
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=0.106 mM for L-ornithine (in the presence of 10 mM 2-oxoglutarate)
CC         {ECO:0000269|PubMed:35337912};
CC         KM=0.211 mM for L-lysine (in the presence of 10 mM 2-oxoglutarate)
CC         {ECO:0000269|PubMed:35337912};
CC         KM=0.446 mM for D-ornithine (in the presence of 5 mM 2-oxoglutarate)
CC         {ECO:0000269|PubMed:35337912};
CC         KM=5.22 mM for D-lysine (in the presence of 20 mM 2-oxoglutarate)
CC         {ECO:0000269|PubMed:35337912};
CC         KM=0.802 mM for 2-oxoglutarate (in the presence of 1 mM L-ornithine)
CC         {ECO:0000269|PubMed:35337912};
CC         KM=0.624 mM for 2-oxoglutarate (in the presence of 2 mM L-lysine)
CC         {ECO:0000269|PubMed:35337912};
CC         KM=0.182 mM for 2-oxoglutarate (in the presence of 5 mM D-ornithine)
CC         {ECO:0000269|PubMed:35337912};
CC         KM=1.23 mM for 2-oxoglutarate (in the presence of 20 mM D-lysine)
CC         {ECO:0000269|PubMed:35337912};
CC         Note=kcat is 4.32 sec(-1) with L-ornithine as substrate. kcat is 1.61
CC         sec(-1) with L-lysine as substrate. kcat is 0.493 sec(-1) with
CC         D-ornithine as substrate. kcat is 3.25 sec(-1) with D-lysine as
CC         substrate. kcat is 3.51 sec(-1) with 2-oxoglutarate as substrate in
CC         the presence of L-ornithine. kcat is 1.41 sec(-1) with 2-oxoglutarate
CC         as substrate in the presence of L-lysine. kcat is 0.462 sec(-1) with
CC         2-oxoglutarate as substrate in the presence of D-ornithine. kcat is
CC         3.02 sec(-1) with 2-oxoglutarate as substrate in the presence of
CC         D-lysine. {ECO:0000269|PubMed:35337912};
CC       pH dependence:
CC         Optimum pH is 6.5-7.0. {ECO:0000269|PubMed:35337912};
CC       Temperature dependence:
CC         Optimum temperature is higher than 90 degrees Celsius.
CC         {ECO:0000269|PubMed:35337912};
CC   -!- SUBUNIT: Homotetramer; dimer of dimers. {ECO:0000269|PubMed:35337912}.
CC   -!- DOMAIN: A 'Glu switch' mechanism prevents L-ornithine from binding in
CC       an orientation that would lead to transamination of the alpha-amino
CC       group (PubMed:35337912). The side-chain of Glu-236 forms a salt bridge
CC       with that of Arg-419, closing the 'Glu switch' and thus preventing
CC       unsuitable L-ornithine binding (PubMed:35337912).
CC       {ECO:0000269|PubMed:35337912}.
CC   -!- SIMILARITY: Belongs to the class-III pyridoxal-phosphate-dependent
CC       aminotransferase family. {ECO:0000305}.
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DR   EMBL; BA000001; BAA30529.1; -; Genomic_DNA.
DR   PIR; A71016; A71016.
DR   RefSeq; WP_010885506.1; NC_000961.1.
DR   PDB; 7VNO; X-ray; 1.80 A; A/B=1-454.
DR   PDB; 7VNT; X-ray; 1.92 A; A/B=1-454.
DR   PDB; 7VO1; X-ray; 2.99 A; A/B=1-454.
DR   PDBsum; 7VNO; -.
DR   PDBsum; 7VNT; -.
DR   PDBsum; 7VO1; -.
DR   AlphaFoldDB; O50131; -.
DR   SMR; O50131; -.
DR   STRING; 70601.gene:9378399; -.
DR   EnsemblBacteria; BAA30529; BAA30529; BAA30529.
DR   GeneID; 1443744; -.
DR   KEGG; pho:PH1423; -.
DR   eggNOG; arCOG00915; Archaea.
DR   OrthoDB; 6534at2157; -.
DR   Proteomes; UP000000752; Chromosome.
DR   GO; GO:0030170; F:pyridoxal phosphate binding; IEA:InterPro.
DR   GO; GO:0008483; F:transaminase activity; IEA:UniProtKB-KW.
DR   CDD; cd00610; OAT_like; 1.
DR   Gene3D; 3.90.1150.10; Aspartate Aminotransferase, domain 1; 1.
DR   Gene3D; 3.40.640.10; Type I PLP-dependent aspartate aminotransferase-like (Major domain); 1.
DR   InterPro; IPR005814; Aminotrans_3.
DR   InterPro; IPR049704; Aminotrans_3_PPA_site.
DR   InterPro; IPR015424; PyrdxlP-dep_Trfase.
DR   InterPro; IPR015421; PyrdxlP-dep_Trfase_major.
DR   InterPro; IPR015422; PyrdxlP-dep_Trfase_small.
DR   PANTHER; PTHR11986; AMINOTRANSFERASE CLASS III; 1.
DR   PANTHER; PTHR11986:SF58; LEUCINE_METHIONINE RACEMASE; 1.
DR   Pfam; PF00202; Aminotran_3; 1.
DR   PIRSF; PIRSF000521; Transaminase_4ab_Lys_Orn; 1.
DR   SUPFAM; SSF53383; PLP-dependent transferases; 1.
DR   PROSITE; PS00600; AA_TRANSFER_CLASS_3; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Aminotransferase; Pyridoxal phosphate; Transferase.
FT   CHAIN           1..454
FT                   /note="Ornithine aminotransferase"
FT                   /id="PRO_0000458674"
FT   BINDING         124
FT                   /ligand="pyridoxal 5'-phosphate"
FT                   /ligand_id="ChEBI:CHEBI:597326"
FT                   /evidence="ECO:0000269|PubMed:35337912,
FT                   ECO:0007744|PDB:7VNO, ECO:0007744|PDB:7VNT"
FT   BINDING         125
FT                   /ligand="pyridoxal 5'-phosphate"
FT                   /ligand_id="ChEBI:CHEBI:597326"
FT                   /evidence="ECO:0000269|PubMed:35337912,
FT                   ECO:0007744|PDB:7VNO, ECO:0007744|PDB:7VNT"
FT   BINDING         267
FT                   /ligand="pyridoxal 5'-phosphate"
FT                   /ligand_id="ChEBI:CHEBI:597326"
FT                   /evidence="ECO:0000269|PubMed:35337912,
FT                   ECO:0007744|PDB:7VNO, ECO:0007744|PDB:7VNT"
FT   BINDING         321
FT                   /ligand="pyridoxal 5'-phosphate"
FT                   /ligand_id="ChEBI:CHEBI:597326"
FT                   /evidence="ECO:0000269|PubMed:35337912,
FT                   ECO:0007744|PDB:7VNO, ECO:0007744|PDB:7VNT"
FT   SITE            93
FT                   /note="Plays critical role in maintaining high affinity for
FT                   the substrate"
FT                   /evidence="ECO:0000305|PubMed:35337912"
FT   MOD_RES         293
FT                   /note="N6-(pyridoxal phosphate)lysine"
FT                   /evidence="ECO:0000269|PubMed:35337912,
FT                   ECO:0007744|PDB:7VNT"
FT   MUTAGEN         92
FT                   /note="T->V: Slightly increases the specific activity.
FT                   Increases KM for L-ornithine."
FT                   /evidence="ECO:0000269|PubMed:35337912"
FT   MUTAGEN         93
FT                   /note="D->L: Reduces the specific activity. Increases KM
FT                   for L-ornithine."
FT                   /evidence="ECO:0000269|PubMed:35337912"
SQ   SEQUENCE   454 AA;  50615 MW;  8B9D64EE3CE11C18 CRC64;
     MELKPNVKEI PGPKARKVIE EHHKYMATTT NDPNEYFLVI ERAEGVYWID VDGNVLLDFS
     SGIGVMNVGL RNPKVIEAIK KQLDLVLHAA GTDYYNPYQV ELAKKLVEIA PGDIERKVFL
     SNSGTEANEA ALKIAKWSTN RKMFIAFIGA FHGRTHGTMS LTASKPVQRS RMFPTMPGVV
     HVPYPNPYRN PWGIDGYENP DELINRVIDY IEEYLFEHYV PAEEVAGIFF EPIQGEGGYV
     VPPKNFFKEL KKLADKHGIL LIDDEVQMGM GRTGRMWAIE HFDIVPDIVT VAKALGGGIP
     IGATIFRADL DFGVSGVHSN TFGGNTVAAA AALAVIEELQ NGLIENAQKL EPLFRERLEE
     MKEKYEIIGD VRGLGLAWGV EFVKDRKTKE YATKERGEIV VEALKRGLAL LGCGKSAIRL
     IPPLIISEEE AKMGLDIFEE AIKVVSERHG YKIH
//