CYB2_TALSN
ID CYB2_TALSN Reviewed; 496 AA.
AC B8MKR3;
DT 23-FEB-2022, integrated into UniProtKB/Swiss-Prot.
DT 03-MAR-2009, sequence version 1.
DT 03-AUG-2022, entry version 67.
DE RecName: Full=L-lactate dehydrogenase (cytochrome);
DE EC=1.1.2.3 {ECO:0000269|PubMed:34555022};
GN ORFNames=TSTA_043820 {ECO:0000312|EMBL:EED14912.1};
OS Talaromyces stipitatus (strain ATCC 10500 / CBS 375.48 / QM 6759 / NRRL
OS 1006) (Penicillium stipitatum).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Trichocomaceae; Talaromyces;
OC Talaromyces sect. Talaromyces.
OX NCBI_TaxID=441959;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 10500 / CBS 375.48 / QM 6759 / NRRL 1006;
RX PubMed=25676766; DOI=10.1128/genomea.01559-14;
RA Nierman W.C., Fedorova-Abrams N.D., Andrianopoulos A.;
RT "Genome sequence of the AIDS-associated pathogen Penicillium marneffei
RT (ATCC18224) and its near taxonomic relative Talaromyces stipitatus
RT (ATCC10500).";
RL Genome Announc. 3:E0155914-E0155914(2015).
RN [2]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=34555022; DOI=10.1371/journal.pcbi.1009446;
RA Rembeza E., Engqvist M.K.M.;
RT "Experimental and computational investigation of enzyme functional
RT annotations uncovers misannotation in the EC 1.1.3.15 enzyme class.";
RL PLoS Comput. Biol. 17:e1009446-e1009446(2021).
CC -!- FUNCTION: Catalyzes the oxidation of (S)-lactate (L-lactate) to
CC pyruvate with subsequent transfer of electrons to cytochrome c. Also
CC displays oxidase activity in vitro, catalyzing the oxidation of a broad
CC range of 2-hydroxyacids, such as glycolate, (S)-lactate, 2-
CC hydroxyoctanoate, (S)-2-hydroxyglutarate and to a lesser extent
CC mandelate, to the corresponding 2-oxoacids, with a reduction of O2 to
CC H2O2 (PubMed:34555022). However, the physiological activity of this
CC enzyme is most likely to function as an L-lactate dehydrogenase. May be
CC involved in the utilization of (S)-lactate as a sole source of carbon
CC for growth (Probable). {ECO:0000269|PubMed:34555022, ECO:0000305}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(S)-lactate + 2 Fe(III)-[cytochrome c] = 2 Fe(II)-[cytochrome
CC c] + 2 H(+) + pyruvate; Xref=Rhea:RHEA:19909, Rhea:RHEA-COMP:10350,
CC Rhea:RHEA-COMP:14399, ChEBI:CHEBI:15361, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16651, ChEBI:CHEBI:29033, ChEBI:CHEBI:29034; EC=1.1.2.3;
CC Evidence={ECO:0000269|PubMed:34555022};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19910;
CC Evidence={ECO:0000305};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a (2S)-2-hydroxycarboxylate + O2 = a 2-oxocarboxylate + H2O2;
CC Xref=Rhea:RHEA:16789, ChEBI:CHEBI:15379, ChEBI:CHEBI:16240,
CC ChEBI:CHEBI:35179, ChEBI:CHEBI:58123;
CC Evidence={ECO:0000269|PubMed:34555022};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=glycolate + O2 = glyoxylate + H2O2; Xref=Rhea:RHEA:25311,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:16240, ChEBI:CHEBI:29805,
CC ChEBI:CHEBI:36655; Evidence={ECO:0000269|PubMed:34555022};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(S)-lactate + O2 = H2O2 + pyruvate; Xref=Rhea:RHEA:55868,
CC ChEBI:CHEBI:15361, ChEBI:CHEBI:15379, ChEBI:CHEBI:16240,
CC ChEBI:CHEBI:16651; Evidence={ECO:0000269|PubMed:34555022};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-hydroxyoctanoate + O2 = 2-oxooctanoate + H2O2;
CC Xref=Rhea:RHEA:67940, ChEBI:CHEBI:15379, ChEBI:CHEBI:16240,
CC ChEBI:CHEBI:133514, ChEBI:CHEBI:176689;
CC Evidence={ECO:0000269|PubMed:34555022};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(S)-2-hydroxyglutarate + O2 = 2-oxoglutarate + H2O2;
CC Xref=Rhea:RHEA:27662, ChEBI:CHEBI:15379, ChEBI:CHEBI:16240,
CC ChEBI:CHEBI:16782, ChEBI:CHEBI:16810;
CC Evidence={ECO:0000269|PubMed:34555022};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=mandelate + O2 = H2O2 + phenylglyoxylate;
CC Xref=Rhea:RHEA:68968, ChEBI:CHEBI:15379, ChEBI:CHEBI:16240,
CC ChEBI:CHEBI:25147, ChEBI:CHEBI:36656;
CC Evidence={ECO:0000269|PubMed:34555022};
CC -!- COFACTOR:
CC Name=FMN; Xref=ChEBI:CHEBI:58210;
CC Evidence={ECO:0000250|UniProtKB:P00175};
CC -!- COFACTOR:
CC Name=heme b; Xref=ChEBI:CHEBI:60344;
CC Evidence={ECO:0000250|UniProtKB:P00175};
CC Note=Binds 1 heme b (iron(II)-protoporphyrin IX) group non-covalently
CC per subunit. {ECO:0000250|UniProtKB:P00175};
CC -!- SUBUNIT: Homotetramer. {ECO:0000250|UniProtKB:P00175}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion intermembrane space
CC {ECO:0000250|UniProtKB:P00175}.
CC -!- DOMAIN: Consists of two discrete domains, an N-terminal cytochrome b
CC domain and a C-terminal flavin-binding domain. The cytochrome b domain
CC is required for efficient cytochrome c reduction.
CC {ECO:0000250|UniProtKB:P00175}.
CC -!- SIMILARITY: In the N-terminal section; belongs to the cytochrome b5
CC family. {ECO:0000305}.
CC -!- SIMILARITY: In the C-terminal section; belongs to the FMN-dependent
CC alpha-hydroxy acid dehydrogenase family. {ECO:0000305}.
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DR EMBL; EQ962657; EED14912.1; -; Genomic_DNA.
DR RefSeq; XP_002484865.1; XM_002484820.1.
DR STRING; 441959.B8MKR3; -.
DR EnsemblFungi; EED14912; EED14912; TSTA_043820.
DR GeneID; 8097890; -.
DR VEuPathDB; FungiDB:TSTA_043820; -.
DR eggNOG; KOG0537; Eukaryota.
DR eggNOG; KOG0538; Eukaryota.
DR HOGENOM; CLU_020639_1_1_1; -.
DR InParanoid; B8MKR3; -.
DR OMA; WVILYGN; -.
DR OrthoDB; 879633at2759; -.
DR PhylomeDB; B8MKR3; -.
DR Proteomes; UP000001745; Unassembled WGS sequence.
DR GO; GO:0005758; C:mitochondrial intermembrane space; IEA:UniProtKB-SubCell.
DR GO; GO:0003973; F:(S)-2-hydroxy-acid oxidase activity; IEA:UniProtKB-EC.
DR GO; GO:0020037; F:heme binding; IEA:InterPro.
DR GO; GO:0004460; F:L-lactate dehydrogenase (cytochrome) activity; IEA:RHEA.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR CDD; cd02922; FCB2_FMN; 1.
DR Gene3D; 3.10.120.10; -; 1.
DR Gene3D; 3.20.20.70; -; 1.
DR InterPro; IPR013785; Aldolase_TIM.
DR InterPro; IPR001199; Cyt_B5-like_heme/steroid-bd.
DR InterPro; IPR036400; Cyt_B5-like_heme/steroid_sf.
DR InterPro; IPR018506; Cyt_B5_heme-BS.
DR InterPro; IPR000262; FMN-dep_DH.
DR InterPro; IPR037396; FMN_HAD.
DR InterPro; IPR037458; L-MDH/L-LDH_FMN-bd.
DR Pfam; PF00173; Cyt-b5; 1.
DR Pfam; PF01070; FMN_dh; 1.
DR PRINTS; PR00363; CYTOCHROMEB5.
DR SMART; SM01117; Cyt-b5; 1.
DR SUPFAM; SSF55856; SSF55856; 1.
DR PROSITE; PS00191; CYTOCHROME_B5_1; 1.
DR PROSITE; PS50255; CYTOCHROME_B5_2; 1.
DR PROSITE; PS51349; FMN_HYDROXY_ACID_DH_2; 1.
PE 1: Evidence at protein level;
KW Flavoprotein; FMN; Heme; Iron; Metal-binding; Mitochondrion;
KW Oxidoreductase; Reference proteome.
FT CHAIN 1..496
FT /note="L-lactate dehydrogenase (cytochrome)"
FT /id="PRO_0000454855"
FT DOMAIN 2..79
FT /note="Cytochrome b5 heme-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00279"
FT DOMAIN 101..478
FT /note="FMN hydroxy acid dehydrogenase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00683"
FT REGION 77..103
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 290..310
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 37
FT /ligand="heme b"
FT /ligand_id="ChEBI:CHEBI:60344"
FT /ligand_part="Fe"
FT /ligand_part_id="ChEBI:CHEBI:18248"
FT /note="axial binding residue"
FT /evidence="ECO:0000250|UniProtKB:P00175"
FT BINDING 60
FT /ligand="heme b"
FT /ligand_id="ChEBI:CHEBI:60344"
FT /ligand_part="Fe"
FT /ligand_part_id="ChEBI:CHEBI:18248"
FT /note="axial binding residue"
FT /evidence="ECO:0000250|UniProtKB:P00175"
FT BINDING 127
FT /ligand="heme b"
FT /ligand_id="ChEBI:CHEBI:60344"
FT /evidence="ECO:0000250|UniProtKB:P00175"
FT BINDING 127
FT /ligand="pyruvate"
FT /ligand_id="ChEBI:CHEBI:15361"
FT /evidence="ECO:0000250|UniProtKB:P00175"
FT BINDING 179..182
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000250|UniProtKB:P00175"
FT BINDING 209
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000250|UniProtKB:P00175"
FT BINDING 232
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000250|UniProtKB:P00175"
FT BINDING 234
FT /ligand="pyruvate"
FT /ligand_id="ChEBI:CHEBI:15361"
FT /evidence="ECO:0000250|UniProtKB:P00175"
FT BINDING 261
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000250|UniProtKB:P00175"
FT BINDING 344
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000250|UniProtKB:P00175"
FT BINDING 370
FT /ligand="pyruvate"
FT /ligand_id="ChEBI:CHEBI:15361"
FT /evidence="ECO:0000250|UniProtKB:P00175"
FT BINDING 373
FT /ligand="pyruvate"
FT /ligand_id="ChEBI:CHEBI:15361"
FT /evidence="ECO:0000250|UniProtKB:P00175"
FT BINDING 404..408
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000250|UniProtKB:P00175"
FT BINDING 427..428
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000250|UniProtKB:P00175"
SQ SEQUENCE 496 AA; 53913 MW; 9E20BE8E81F07C69 CRC64;
MARVLDAAEV AKHNTPESCW VILYGKVYDV TEFISSHPGG VKVILRLAGT DATEEYDPIH
PPGTLEENLK PEALLGTVDP ETLPKPDKQQ SSPEEEEQGP PPMETLFNLD EIEQVATKQV
SRKAWGYYYS AADDLISKNF NREIYRSILL RPRVFIDVGK CDLSTTILGH RVGLPIYISP
AAMARLAHPA GEAGIAAACR GFGAMQMISN NASMSPEQIV ENAAPDQVFG WQLYVQMERK
KSEAMLARVE KLKAIKCVIL TLDAPVPGKR EDDMRTDNIG KKLPVSSAKV AEKEVETLPD
GTPVPTDGGG GVGKQLFAGT AYDLTWKETL TWLTKVTKLP IILKGLQTHE DAYIASLYAP
QVKGIILSNH GGRALDTAPP AVHTLLEIRK YCPEVFDKIE VLVDGGIRRG TDVVKALCLG
ARAVGIGRPA LWGLGAGGIA GVERTLEILA DETKTCMQLL GVEKISDLGP EYINSRIVEQ
QIYDGPSGLE KARAKL
