HKT_ANOGA
ID HKT_ANOGA Reviewed; 396 AA.
AC Q7PRG3; Q4LAM2;
DT 07-APR-2021, integrated into UniProtKB/Swiss-Prot.
DT 09-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 156.
DE RecName: Full=3-hydroxykynurenine transaminase {ECO:0000303|PubMed:16262702};
DE EC=2.6.1.63 {ECO:0000269|PubMed:16262702};
DE AltName: Full=AgHKT {ECO:0000303|PubMed:16585514};
DE AltName: Full=Alanine--glyoxylate aminotransferase {ECO:0000255|PIRNR:PIRNR000524};
DE EC=2.6.1.44 {ECO:0000250|UniProtKB:Q0IG34};
GN Name=HKT {ECO:0000303|PubMed:16585514};
GN Synonyms=1272658, 3hkt {ECO:0000303|PubMed:16262702};
GN ORFNames=AgaP_AGAP010387 {ECO:0000312|EMBL:EAA07245.4};
OS Anopheles gambiae (African malaria mosquito).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Nematocera; Culicoidea; Culicidae;
OC Anophelinae; Anopheles.
OX NCBI_TaxID=7165 {ECO:0000312|Proteomes:UP000007062};
RN [1] {ECO:0000312|EMBL:CAJ14970.1}
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, COFACTOR,
RP BIOPHYSICOCHEMICAL PROPERTIES, PATHWAY, SUBUNIT, TISSUE SPECIFICITY, AND
RP DEVELOPMENTAL STAGE.
RX PubMed=16262702; DOI=10.1111/j.1742-4658.2005.04961.x;
RA Rossi F., Lombardo F., Paglino A., Cassani C., Miglio G., Arca B.,
RA Rizzi M.;
RT "Identification and biochemical characterization of the Anopheles gambiae
RT 3-hydroxykynurenine transaminase.";
RL FEBS J. 272:5653-5662(2005).
RN [2] {ECO:0000312|Proteomes:UP000007062}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=PEST {ECO:0000312|Proteomes:UP000007062};
RX PubMed=12364791; DOI=10.1126/science.1076181;
RA Holt R.A., Subramanian G.M., Halpern A., Sutton G.G., Charlab R.,
RA Nusskern D.R., Wincker P., Clark A.G., Ribeiro J.M.C., Wides R.,
RA Salzberg S.L., Loftus B.J., Yandell M.D., Majoros W.H., Rusch D.B., Lai Z.,
RA Kraft C.L., Abril J.F., Anthouard V., Arensburger P., Atkinson P.W.,
RA Baden H., de Berardinis V., Baldwin D., Benes V., Biedler J., Blass C.,
RA Bolanos R., Boscus D., Barnstead M., Cai S., Center A., Chaturverdi K.,
RA Christophides G.K., Chrystal M.A.M., Clamp M., Cravchik A., Curwen V.,
RA Dana A., Delcher A., Dew I., Evans C.A., Flanigan M.,
RA Grundschober-Freimoser A., Friedli L., Gu Z., Guan P., Guigo R.,
RA Hillenmeyer M.E., Hladun S.L., Hogan J.R., Hong Y.S., Hoover J.,
RA Jaillon O., Ke Z., Kodira C.D., Kokoza E., Koutsos A., Letunic I.,
RA Levitsky A.A., Liang Y., Lin J.-J., Lobo N.F., Lopez J.R., Malek J.A.,
RA McIntosh T.C., Meister S., Miller J.R., Mobarry C., Mongin E., Murphy S.D.,
RA O'Brochta D.A., Pfannkoch C., Qi R., Regier M.A., Remington K., Shao H.,
RA Sharakhova M.V., Sitter C.D., Shetty J., Smith T.J., Strong R., Sun J.,
RA Thomasova D., Ton L.Q., Topalis P., Tu Z.J., Unger M.F., Walenz B.,
RA Wang A.H., Wang J., Wang M., Wang X., Woodford K.J., Wortman J.R., Wu M.,
RA Yao A., Zdobnov E.M., Zhang H., Zhao Q., Zhao S., Zhu S.C., Zhimulev I.,
RA Coluzzi M., della Torre A., Roth C.W., Louis C., Kalush F., Mural R.J.,
RA Myers E.W., Adams M.D., Smith H.O., Broder S., Gardner M.J., Fraser C.M.,
RA Birney E., Bork P., Brey P.T., Venter J.C., Weissenbach J., Kafatos F.C.,
RA Collins F.H., Hoffman S.L.;
RT "The genome sequence of the malaria mosquito Anopheles gambiae.";
RL Science 298:129-149(2002).
RN [3] {ECO:0000312|EMBL:EAA07245.4}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=PEST {ECO:0000312|EMBL:EAA07245.4};
RX PubMed=17210077; DOI=10.1186/gb-2007-8-1-r5;
RA Sharakhova M.V., Hammond M.P., Lobo N.F., Krzywinski J., Unger M.F.,
RA Hillenmeyer M.E., Bruggner R.V., Birney E., Collins F.H.;
RT "Update of the Anopheles gambiae PEST genome assembly.";
RL Genome Biol. 8:R5.1-R5.13(2007).
RN [4] {ECO:0007744|PDB:2CH1, ECO:0007744|PDB:2CH2}
RP X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) IN COMPLEX WITH PYRIDOXAL
RP 5-PHOSPHATE AND INHIBITOR.
RX PubMed=16585514; DOI=10.1073/pnas.0510233103;
RA Rossi F., Garavaglia S., Giovenzana G.B., Arca B., Li J., Rizzi M.;
RT "Crystal structure of the Anopheles gambiae 3-hydroxykynurenine
RT transaminase.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:5711-5716(2006).
CC -!- FUNCTION: Catalyzes the pyridoxal 5'-phosphate-dependent transamination
CC of both 3-hydroxykynurenine and L-kynurenine to xanthurenic acid and
CC kynurenic acid, respectively, preferentially using the alpha-ketoacid
CC glyoxylate as the amino group acceptor (PubMed:16262702). Although
CC glyoxylate is the preferred amino group acceptor, transamination of 3-
CC hydroxykynurenine also works with pyruvate as the amino acceptor in
CC vitro (PubMed:16262702). Involved in the detoxification of cytotoxic
CC metabolite 3-hydroxykynurenine generated by the hydroxylation of L-
CC kynurenine, an intermediate in the tryptophan catabolism pathway
CC (PubMed:16262702). The Plasmodium parasite uses xanthurenic acid
CC produced in the midgut to activate its gametocytes ingested during a
CC blood meal (Probable). Also catalyzes, although with a lesser
CC efficiency, the transamination of alanine with glyoxylate as an amino
CC group acceptor (By similarity). May play a role in the detoxification
CC of glyoxylate, a toxic plant metabolite from the diet (By similarity).
CC {ECO:0000250|UniProtKB:Q0IG34, ECO:0000269|PubMed:16262702,
CC ECO:0000305|PubMed:16262702}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=glyoxylate + L-kynurenine = glycine + H2O + kynurenate;
CC Xref=Rhea:RHEA:65896, ChEBI:CHEBI:15377, ChEBI:CHEBI:36655,
CC ChEBI:CHEBI:57305, ChEBI:CHEBI:57959, ChEBI:CHEBI:58454; EC=2.6.1.63;
CC Evidence={ECO:0000269|PubMed:16262702};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3-hydroxy-L-kynurenine + glyoxylate = glycine + H2O +
CC xanthurenate; Xref=Rhea:RHEA:65900, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:36655, ChEBI:CHEBI:57305, ChEBI:CHEBI:58125,
CC ChEBI:CHEBI:71201; EC=2.6.1.63;
CC Evidence={ECO:0000269|PubMed:16262702};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3-hydroxy-L-kynurenine + pyruvate = H2O + L-alanine +
CC xanthurenate; Xref=Rhea:RHEA:65908, ChEBI:CHEBI:15361,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:57972, ChEBI:CHEBI:58125,
CC ChEBI:CHEBI:71201; Evidence={ECO:0000269|PubMed:16262702};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=glyoxylate + L-alanine = glycine + pyruvate;
CC Xref=Rhea:RHEA:24248, ChEBI:CHEBI:15361, ChEBI:CHEBI:36655,
CC ChEBI:CHEBI:57305, ChEBI:CHEBI:57972; EC=2.6.1.44;
CC Evidence={ECO:0000250|UniProtKB:Q0IG34};
CC -!- COFACTOR:
CC Name=pyridoxal 5'-phosphate; Xref=ChEBI:CHEBI:597326;
CC Evidence={ECO:0000255|PIRNR:PIRNR000524,
CC ECO:0000255|RuleBase:RU004504, ECO:0000269|PubMed:16262702,
CC ECO:0000269|PubMed:16585514};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=2 mM for D,L-3-hydroxykynurenine (at 50 degrees Celsius, pH 7 and
CC with glyoxylate as cosubstrate) {ECO:0000269|PubMed:16262702};
CC KM=2.3 mM for D,L-kynurenine (at 50 degrees Celsius, pH 7 and with
CC glyoxylate as cosubstrate) {ECO:0000269|PubMed:16262702};
CC KM=1 mM for L-kynurenine (at 50 degrees Celsius, pH 7 and with
CC glyoxylate as cosubstrate) {ECO:0000269|PubMed:16262702};
CC KM=2.7 mM for glyoxylate (at 50 degrees Celsius, pH 7 and with D,L-3-
CC hydroxykynurenine as cosubstrate) {ECO:0000269|PubMed:16262702};
CC Note=kcat is 988.5 min(-1) for D,L-3-hydroxykynurenine (at 50 degrees
CC Celsius, pH 7 and with glyoxylate as cosubstrate) (PubMed:16262702).
CC kcat is 1077.2 min(-1) for D,L-kynurenine (at 50 degrees Celsius, pH
CC 7 and with glyoxylate as cosubstrate) (PubMed:16262702). kcat is
CC 611.5 min(-1) for L-kynurenine (at 50 degrees Celsius, pH 7 and with
CC glyoxylate as cosubstrate) (PubMed:16262702). kcat is 2264.8 min(-1)
CC for glyoxylate (at 50 degrees Celsius, pH 7 and with D,L-3-
CC hydroxykynurenine as cosubstrate) (PubMed:16262702).
CC {ECO:0000269|PubMed:16262702};
CC pH dependence:
CC Optimum pH is 7.8. {ECO:0000269|PubMed:16262702};
CC Temperature dependence:
CC Optimum temperature is 60 degrees Celsius (PubMed:16262702). At
CC physiological temperatures (30 degrees Celsius), retains 60-65% of
CC its activity (PubMed:16262702). {ECO:0000269|PubMed:16262702};
CC -!- PATHWAY: Amino-acid degradation; L-kynurenine degradation; kynurenate
CC from L-kynurenine: step 1/2. {ECO:0000269|PubMed:16262702}.
CC -!- SUBUNIT: Homodimer. {ECO:0000305|PubMed:16262702}.
CC -!- SUBCELLULAR LOCATION: Peroxisome {ECO:0000250|UniProtKB:P21549}.
CC -!- TISSUE SPECIFICITY: Expressed in gut and ovaries.
CC {ECO:0000269|PubMed:16262702}.
CC -!- DEVELOPMENTAL STAGE: Expressed throughout embryonic and larval stages
CC and in both adult males and females (PubMed:16262702). Expression is
CC very low during the pupal stage (PubMed:16262702).
CC {ECO:0000269|PubMed:16262702}.
CC -!- SIMILARITY: Belongs to the class-V pyridoxal-phosphate-dependent
CC aminotransferase family. {ECO:0000255|PIRNR:PIRNR000524,
CC ECO:0000255|RuleBase:RU004075}.
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DR EMBL; AM042695; CAJ14970.1; -; mRNA.
DR EMBL; AAAB01008849; EAA07245.4; -; Genomic_DNA.
DR RefSeq; XP_311559.3; XM_311559.4.
DR PDB; 2CH1; X-ray; 2.40 A; A/B/C/D=1-396.
DR PDB; 2CH2; X-ray; 2.70 A; A/B/C/D=1-396.
DR PDBsum; 2CH1; -.
DR PDBsum; 2CH2; -.
DR AlphaFoldDB; Q7PRG3; -.
DR SMR; Q7PRG3; -.
DR DIP; DIP-61154N; -.
DR STRING; 7165.AGAP010387-PC; -.
DR PaxDb; Q7PRG3; -.
DR GeneID; 1272658; -.
DR KEGG; aga:AgaP_AGAP010387; -.
DR VEuPathDB; VectorBase:AGAP010387; -.
DR eggNOG; KOG2862; Eukaryota.
DR InParanoid; Q7PRG3; -.
DR OMA; AHMGHVN; -.
DR OrthoDB; 984738at2759; -.
DR PhylomeDB; Q7PRG3; -.
DR UniPathway; UPA00334; UER00726.
DR EvolutionaryTrace; Q7PRG3; -.
DR Proteomes; UP000007062; Chromosome 3L.
DR GO; GO:0005777; C:peroxisome; IBA:GO_Central.
DR GO; GO:0008453; F:alanine-glyoxylate transaminase activity; IDA:UniProtKB.
DR GO; GO:0036137; F:kynurenine aminotransferase activity; IDA:UniProtKB.
DR GO; GO:0047315; F:kynurenine-glyoxylate transaminase activity; IEA:UniProtKB-EC.
DR GO; GO:0030170; F:pyridoxal phosphate binding; IDA:UniProtKB.
DR GO; GO:0004760; F:serine-pyruvate transaminase activity; IBA:GO_Central.
DR GO; GO:0019265; P:glycine biosynthetic process, by transamination of glyoxylate; IBA:GO_Central.
DR GO; GO:0009436; P:glyoxylate catabolic process; IDA:UniProtKB.
DR GO; GO:0097053; P:L-kynurenine catabolic process; IDA:UniProtKB.
DR Gene3D; 3.40.640.10; -; 1.
DR Gene3D; 3.90.1150.10; -; 1.
DR InterPro; IPR000192; Aminotrans_V_dom.
DR InterPro; IPR020578; Aminotrans_V_PyrdxlP_BS.
DR InterPro; IPR015424; PyrdxlP-dep_Trfase.
DR InterPro; IPR015421; PyrdxlP-dep_Trfase_major.
DR InterPro; IPR015422; PyrdxlP-dep_Trfase_small.
DR InterPro; IPR024169; SP_NH2Trfase/AEP_transaminase.
DR Pfam; PF00266; Aminotran_5; 1.
DR PIRSF; PIRSF000524; SPT; 1.
DR SUPFAM; SSF53383; SSF53383; 1.
DR PROSITE; PS00595; AA_TRANSFER_CLASS_5; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Aminotransferase; Peroxisome; Pyridoxal phosphate;
KW Reference proteome; Transferase.
FT CHAIN 1..396
FT /note="3-hydroxykynurenine transaminase"
FT /id="PRO_0000452184"
FT REGION 43..44
FT /note="Binds to and confers specificity for 3-
FT hydroxykynurenine; shared with dimeric partner"
FT /evidence="ECO:0000305|PubMed:16585514,
FT ECO:0007744|PDB:2CH2"
FT BINDING 77..79
FT /ligand="pyridoxal 5'-phosphate"
FT /ligand_id="ChEBI:CHEBI:597326"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000269|PubMed:16585514,
FT ECO:0007744|PDB:2CH1, ECO:0007744|PDB:2CH2"
FT BINDING 154
FT /ligand="pyridoxal 5'-phosphate"
FT /ligand_id="ChEBI:CHEBI:597326"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000269|PubMed:16585514,
FT ECO:0007744|PDB:2CH1, ECO:0007744|PDB:2CH2"
FT BINDING 154
FT /ligand="substrate"
FT /evidence="ECO:0000305|PubMed:16585514,
FT ECO:0007744|PDB:2CH2"
FT BINDING 204
FT /ligand="pyridoxal 5'-phosphate"
FT /ligand_id="ChEBI:CHEBI:597326"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000269|PubMed:16585514,
FT ECO:0007744|PDB:2CH1, ECO:0007744|PDB:2CH2"
FT BINDING 256
FT /ligand="pyridoxal 5'-phosphate"
FT /ligand_id="ChEBI:CHEBI:597326"
FT /ligand_note="ligand shared between dimeric partners"
FT /evidence="ECO:0000269|PubMed:16585514,
FT ECO:0007744|PDB:2CH1, ECO:0007744|PDB:2CH2"
FT BINDING 259
FT /ligand="pyridoxal 5'-phosphate"
FT /ligand_id="ChEBI:CHEBI:597326"
FT /ligand_note="ligand shared between dimeric partners"
FT /evidence="ECO:0000269|PubMed:16585514,
FT ECO:0007744|PDB:2CH1, ECO:0007744|PDB:2CH2"
FT BINDING 356
FT /ligand="substrate"
FT /evidence="ECO:0000305|PubMed:16585514,
FT ECO:0007744|PDB:2CH2"
FT MOD_RES 205
FT /note="N6-(pyridoxal phosphate)lysine"
FT /evidence="ECO:0000269|PubMed:16585514,
FT ECO:0007744|PDB:2CH1, ECO:0007744|PDB:2CH2"
FT HELIX 8..10
FT /evidence="ECO:0007829|PDB:2CH1"
FT STRAND 23..26
FT /evidence="ECO:0007829|PDB:2CH1"
FT HELIX 31..36
FT /evidence="ECO:0007829|PDB:2CH1"
FT HELIX 47..64
FT /evidence="ECO:0007829|PDB:2CH1"
FT STRAND 71..76
FT /evidence="ECO:0007829|PDB:2CH1"
FT HELIX 78..89
FT /evidence="ECO:0007829|PDB:2CH1"
FT STRAND 95..102
FT /evidence="ECO:0007829|PDB:2CH1"
FT HELIX 103..114
FT /evidence="ECO:0007829|PDB:2CH1"
FT STRAND 118..123
FT /evidence="ECO:0007829|PDB:2CH1"
FT HELIX 132..142
FT /evidence="ECO:0007829|PDB:2CH1"
FT STRAND 145..153
FT /evidence="ECO:0007829|PDB:2CH1"
FT TURN 154..157
FT /evidence="ECO:0007829|PDB:2CH1"
FT HELIX 165..171
FT /evidence="ECO:0007829|PDB:2CH1"
FT STRAND 175..179
FT /evidence="ECO:0007829|PDB:2CH1"
FT TURN 181..183
FT /evidence="ECO:0007829|PDB:2CH1"
FT TURN 191..195
FT /evidence="ECO:0007829|PDB:2CH1"
FT STRAND 198..200
FT /evidence="ECO:0007829|PDB:2CH1"
FT TURN 203..207
FT /evidence="ECO:0007829|PDB:2CH1"
FT STRAND 214..218
FT /evidence="ECO:0007829|PDB:2CH1"
FT HELIX 220..227
FT /evidence="ECO:0007829|PDB:2CH1"
FT HELIX 236..238
FT /evidence="ECO:0007829|PDB:2CH1"
FT HELIX 240..246
FT /evidence="ECO:0007829|PDB:2CH1"
FT STRAND 250..252
FT /evidence="ECO:0007829|PDB:2CH1"
FT HELIX 262..278
FT /evidence="ECO:0007829|PDB:2CH1"
FT HELIX 280..301
FT /evidence="ECO:0007829|PDB:2CH1"
FT STRAND 305..307
FT /evidence="ECO:0007829|PDB:2CH1"
FT HELIX 310..312
FT /evidence="ECO:0007829|PDB:2CH1"
FT STRAND 317..321
FT /evidence="ECO:0007829|PDB:2CH1"
FT HELIX 328..339
FT /evidence="ECO:0007829|PDB:2CH1"
FT HELIX 348..350
FT /evidence="ECO:0007829|PDB:2CH1"
FT TURN 351..353
FT /evidence="ECO:0007829|PDB:2CH1"
FT STRAND 354..358
FT /evidence="ECO:0007829|PDB:2CH1"
FT HELIX 361..363
FT /evidence="ECO:0007829|PDB:2CH1"
FT HELIX 366..383
FT /evidence="ECO:0007829|PDB:2CH1"
SQ SEQUENCE 396 AA; 44298 MW; F323DC64448CFEDC CRC64;
MKFTPPPASL RNPLIIPEKI MMGPGPSNCS KRVLTAMTNT VLSNFHAELF RTMDEVKDGL
RYIFQTENRA TMCVSGSAHA GMEAMLSNLL EEGDRVLIAV NGIWAERAVE MSERYGADVR
TIEGPPDRPF SLETLARAIE LHQPKCLFLT HGDSSSGLLQ PLEGVGQICH QHDCLLIVDA
VASLCGVPFY MDKWEIDAVY TGAQKVLGAP PGITPISISP KALDVIRNRR TKSKVFYWDL
LLLGNYWGCY DEPKRYHHTV ASNLIFALRE ALAQIAEEGL ENQIKRRIEC AQILYEGLGK
MGLDIFVKDP RHRLPTVTGI MIPKGVDWWK VSQYAMNNFS LEVQGGLGPT FGKAWRVGIM
GECSTVQKIQ FYLYGFKESL KATHPDYIFE ESNGFH
