ID V5X964_MYCNE Unreviewed; 575 AA.
AC V5X964;
DT 19-FEB-2014, integrated into UniProtKB/TrEMBL.
DT 19-FEB-2014, sequence version 1.
DT 24-JAN-2024, entry version 39.
DE RecName: Full=Pyruvate dehydrogenase [ubiquinone] {ECO:0000256|HAMAP-Rule:MF_00850};
DE EC=1.2.5.1 {ECO:0000256|HAMAP-Rule:MF_00850};
DE AltName: Full=Pyruvate oxidase {ECO:0000256|HAMAP-Rule:MF_00850};
DE Short=POX {ECO:0000256|HAMAP-Rule:MF_00850};
DE AltName: Full=Pyruvate:ubiquinone-8 oxidoreductase {ECO:0000256|HAMAP-Rule:MF_00850};
GN Name=poxB {ECO:0000256|HAMAP-Rule:MF_00850};
GN ORFNames=D174_10575 {ECO:0000313|EMBL:AHC24995.1};
OS Mycolicibacterium neoaurum VKM Ac-1815D.
OC Bacteria; Actinomycetota; Actinomycetes; Mycobacteriales; Mycobacteriaceae;
OC Mycolicibacterium.
OX NCBI_TaxID=700508 {ECO:0000313|EMBL:AHC24995.1, ECO:0000313|Proteomes:UP000018763};
RN [1] {ECO:0000313|EMBL:AHC24995.1, ECO:0000313|Proteomes:UP000018763}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=VKM Ac-1815D {ECO:0000313|EMBL:AHC24995.1,
RC ECO:0000313|Proteomes:UP000018763};
RX PubMed=24435872;
RA Shtratnikova V.Y., Bragin E.Y., Dovbnya D.V., Pekov Y.A., Schelkunov M.I.,
RA Strizhov N., Ivashina T.V., Ashapkin V.V., Donova M.V.;
RT "Complete Genome Sequence of Sterol-Transforming Mycobacterium neoaurum
RT Strain VKM Ac-1815D.";
RL Genome Announc. 2:e01177-13(2014).
CC -!- FUNCTION: A peripheral cell membrane enzyme that catalyzes the
CC oxidative decarboxylation of pyruvate to form acetate and CO(2). It
CC channels electrons from the cytoplasm to the respiratory chain at the
CC cell membrane via ubiquinone. {ECO:0000256|HAMAP-Rule:MF_00850}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a ubiquinone + H2O + pyruvate = a ubiquinol + acetate + CO2;
CC Xref=Rhea:RHEA:27405, Rhea:RHEA-COMP:9565, Rhea:RHEA-COMP:9566,
CC ChEBI:CHEBI:15361, ChEBI:CHEBI:15377, ChEBI:CHEBI:16389,
CC ChEBI:CHEBI:16526, ChEBI:CHEBI:17976, ChEBI:CHEBI:30089; EC=1.2.5.1;
CC Evidence={ECO:0000256|HAMAP-Rule:MF_00850};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000256|HAMAP-Rule:MF_00850};
CC Note=Binds 1 FAD per subunit. {ECO:0000256|HAMAP-Rule:MF_00850};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000256|HAMAP-Rule:MF_00850};
CC Note=Binds 1 Mg(2+) ion per subunit. {ECO:0000256|HAMAP-Rule:MF_00850};
CC -!- COFACTOR:
CC Name=thiamine diphosphate; Xref=ChEBI:CHEBI:58937;
CC Evidence={ECO:0000256|HAMAP-Rule:MF_00850};
CC Note=Binds 1 thiamine pyrophosphate per subunit. {ECO:0000256|HAMAP-
CC Rule:MF_00850};
CC -!- ACTIVITY REGULATION: The C-terminus inhibits activity; it has to move
CC for the enzyme to be active. Activated by lipid-binding, which occurs
CC via the C-terminus. {ECO:0000256|HAMAP-Rule:MF_00850}.
CC -!- SUBUNIT: Homotetramer. {ECO:0000256|HAMAP-Rule:MF_00850}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000256|HAMAP-Rule:MF_00850};
CC Peripheral membrane protein {ECO:0000256|HAMAP-Rule:MF_00850};
CC Cytoplasmic side {ECO:0000256|HAMAP-Rule:MF_00850}.
CC -!- DOMAIN: Has 4 domains; the Pyr domain which binds the pyrimidine moiety
CC of the thiamine pyrophosphate cofactor, the FAD-binding domain, the PP-
CC binding domain which binds the pyrophosphate portion of thiamine
CC pyrophosphate and the C-terminal membrane binding region. The C-
CC terminus is held closely against the rest of the protein and covers the
CC active site; during activation it unfolds from the rest of the protein
CC and forms an amphipathic helix upon membrane binding, exposing the
CC active site. {ECO:0000256|HAMAP-Rule:MF_00850}.
CC -!- SIMILARITY: Belongs to the TPP enzyme family.
CC {ECO:0000256|ARBA:ARBA00007812, ECO:0000256|HAMAP-Rule:MF_00850,
CC ECO:0000256|RuleBase:RU362132}.
CC -!- CAUTION: Lacks conserved residue(s) required for the propagation of
CC feature annotation. {ECO:0000256|HAMAP-Rule:MF_00850}.
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DR EMBL; CP006936; AHC24995.1; -; Genomic_DNA.
DR RefSeq; WP_019513580.1; NC_023036.2.
DR AlphaFoldDB; V5X964; -.
DR KEGG; mne:D174_10575; -.
DR eggNOG; COG0028; Bacteria.
DR HOGENOM; CLU_013748_3_0_11; -.
DR Proteomes; UP000018763; Chromosome.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0050660; F:flavin adenine dinucleotide binding; IEA:UniProtKB-UniRule.
DR GO; GO:0008289; F:lipid binding; IEA:UniProtKB-UniRule.
DR GO; GO:0000287; F:magnesium ion binding; IEA:UniProtKB-UniRule.
DR GO; GO:0052737; F:pyruvate dehydrogenase (quinone) activity; IEA:UniProtKB-UniRule.
DR GO; GO:0030976; F:thiamine pyrophosphate binding; IEA:UniProtKB-UniRule.
DR GO; GO:0048039; F:ubiquinone binding; IEA:UniProtKB-UniRule.
DR GO; GO:0042867; P:pyruvate catabolic process; IEA:UniProtKB-UniRule.
DR CDD; cd02014; TPP_POX; 1.
DR CDD; cd07039; TPP_PYR_POX; 1.
DR Gene3D; 3.40.50.970; -; 2.
DR Gene3D; 3.40.50.1220; TPP-binding domain; 1.
DR HAMAP; MF_00850; POX; 1.
DR InterPro; IPR029035; DHS-like_NAD/FAD-binding_dom.
DR InterPro; IPR047211; POXB-like.
DR InterPro; IPR044261; Pyruvate_dehydrogenase.
DR InterPro; IPR029061; THDP-binding.
DR InterPro; IPR012000; Thiamin_PyroP_enz_cen_dom.
DR InterPro; IPR012001; Thiamin_PyroP_enz_TPP-bd_dom.
DR InterPro; IPR011766; TPP_enzyme_TPP-bd.
DR InterPro; IPR047212; TPP_POXB-like.
DR InterPro; IPR047210; TPP_PYR_POXB-like.
DR PANTHER; PTHR42981; PYRUVATE DEHYDROGENASE [UBIQUINONE]; 1.
DR PANTHER; PTHR42981:SF2; PYRUVATE DEHYDROGENASE [UBIQUINONE]; 1.
DR Pfam; PF02775; TPP_enzyme_C; 1.
DR Pfam; PF00205; TPP_enzyme_M; 1.
DR Pfam; PF02776; TPP_enzyme_N; 1.
DR SUPFAM; SSF52467; DHS-like NAD/FAD-binding domain; 1.
DR SUPFAM; SSF52518; Thiamin diphosphate-binding fold (THDP-binding); 2.
PE 3: Inferred from homology;
KW Cell membrane {ECO:0000256|HAMAP-Rule:MF_00850};
KW FAD {ECO:0000256|HAMAP-Rule:MF_00850};
KW Flavoprotein {ECO:0000256|HAMAP-Rule:MF_00850};
KW Lipid-binding {ECO:0000256|HAMAP-Rule:MF_00850};
KW Magnesium {ECO:0000256|HAMAP-Rule:MF_00850};
KW Membrane {ECO:0000256|HAMAP-Rule:MF_00850};
KW Metal-binding {ECO:0000256|HAMAP-Rule:MF_00850};
KW Nucleotide-binding {ECO:0000256|HAMAP-Rule:MF_00850};
KW Oxidoreductase {ECO:0000256|HAMAP-Rule:MF_00850};
KW Pyruvate {ECO:0000256|HAMAP-Rule:MF_00850, ECO:0000313|EMBL:AHC24995.1};
KW Reference proteome {ECO:0000313|Proteomes:UP000018763};
KW Thiamine pyrophosphate {ECO:0000256|HAMAP-Rule:MF_00850,
KW ECO:0000256|RuleBase:RU362132};
KW Ubiquinone {ECO:0000256|HAMAP-Rule:MF_00850}.
FT DOMAIN 3..114
FT /note="Thiamine pyrophosphate enzyme N-terminal TPP-
FT binding"
FT /evidence="ECO:0000259|Pfam:PF02776"
FT DOMAIN 190..316
FT /note="Thiamine pyrophosphate enzyme central"
FT /evidence="ECO:0000259|Pfam:PF00205"
FT DOMAIN 378..524
FT /note="Thiamine pyrophosphate enzyme TPP-binding"
FT /evidence="ECO:0000259|Pfam:PF02775"
FT REGION 180..331
FT /note="FAD-binding domain"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_00850"
FT REGION 530..571
FT /note="Membrane-binding domain"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_00850"
FT BINDING 49
FT /ligand="thiamine diphosphate"
FT /ligand_id="ChEBI:CHEBI:58937"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_00850"
FT BINDING 248..251
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_00850"
FT BINDING 271..275
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_00850"
FT BINDING 289
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_00850"
FT BINDING 405..407
FT /ligand="thiamine diphosphate"
FT /ligand_id="ChEBI:CHEBI:58937"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_00850"
FT BINDING 432..434
FT /ligand="thiamine diphosphate"
FT /ligand_id="ChEBI:CHEBI:58937"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_00850"
FT BINDING 432
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_00850"
FT BINDING 459..465
FT /ligand="thiamine diphosphate"
FT /ligand_id="ChEBI:CHEBI:58937"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_00850"
FT BINDING 459
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_00850"
FT SITE 464
FT /note="Moves into active site upon enzyme activation, plays
FT a role in electron transfer"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_00850"
SQ SEQUENCE 575 AA; 61855 MW; D599D7F8D4C51AD0 CRC64;
MTTVADHVIS TLYAGGVSRI YGLPGDSLNG LTDAIRRAEG FSWEHVRHEE TAGFAAAADA
ALTGRLAVCA GSCGPGNLHL INGLFDAQRS RVPVLAIAAH IPQSEIGSEY FQETHPQELF
RECSVYCELV TTAESAPRVL GMAMRAAIAE NGVAVVVVPG EVFLHKTDAL VAPVLATHSI
TRPTDDELLR AATILNGSDK ITVLAGAGAE GAHDDLVRLA ATLQAPVVHA LRGKEFVEYD
NPYDVGMTGL LGFASGYKAI KEAEVLLMLG TDFPYRQFYP ENAVVIQLDI RGRNIGRRTH
VDLPLVGSVS DTLPALTPLL TPKSDRTHLD RSLRHYAKTR RRLDELAAND RDRTPIRPEH
LAAVANRLAA EDAVFTVDVG SPVVWAARYL TMNGRRRLLG SFNHGTMACA LPLAIGAQTV
DRDRQVVAFA GDGGLTMLFG ELITLSQNRL PVKVIVFNNS SLNFVELEMK AAGIVTFGTD
LHNPDFAAVA RSLGLFGRRV EQPGDLEAAL TDAFAHDGPA LIDVVTARQE LSIPPAITVE
QAKGFSLYAI RTIMAGRSDE LLDLVSTNVA RRILD
//