FHMAD_MYCTU
ID FHMAD_MYCTU Reviewed; 360 AA.
AC P96809; F2GLS9; I6Y6Z3; L0T5M8;
DT 09-DEC-2015, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1997, sequence version 1.
DT 03-AUG-2022, entry version 136.
DE RecName: Full=F420-dependent hydroxymycolic acid dehydrogenase {ECO:0000303|PubMed:24349169};
DE Short=fHMAD {ECO:0000303|PubMed:24349169};
DE EC=1.1.98.- {ECO:0000269|PubMed:24349169};
DE AltName: Full=FGD2 {ECO:0000303|PubMed:23110042};
DE Flags: Precursor;
GN Name=fgd2 {ECO:0000312|EMBL:CCP42857.1};
GN OrderedLocusNames=Rv0132c {ECO:0000312|EMBL:CCP42857.1},
GN LH57_00740 {ECO:0000312|EMBL:AIR12853.1};
OS Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv).
OC Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae;
OC Mycobacterium; Mycobacterium tuberculosis complex.
OX NCBI_TaxID=83332;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=9634230; DOI=10.1038/31159;
RA Cole S.T., Brosch R., Parkhill J., Garnier T., Churcher C.M., Harris D.E.,
RA Gordon S.V., Eiglmeier K., Gas S., Barry C.E. III, Tekaia F., Badcock K.,
RA Basham D., Brown D., Chillingworth T., Connor R., Davies R.M., Devlin K.,
RA Feltwell T., Gentles S., Hamlin N., Holroyd S., Hornsby T., Jagels K.,
RA Krogh A., McLean J., Moule S., Murphy L.D., Oliver S., Osborne J.,
RA Quail M.A., Rajandream M.A., Rogers J., Rutter S., Seeger K., Skelton S.,
RA Squares S., Squares R., Sulston J.E., Taylor K., Whitehead S.,
RA Barrell B.G.;
RT "Deciphering the biology of Mycobacterium tuberculosis from the complete
RT genome sequence.";
RL Nature 393:537-544(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 27294 / TMC 102 / H37Rv;
RA Hazbon M.H., Riojas M.A., Damon A.M., Alalade R.O., Cantwell B.J.,
RA Monaco A., King S., Sohrabi A.;
RT "Phylogenetic analysis of Mycobacterial species using whole genome
RT sequences.";
RL Submitted (SEP-2014) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP ACTIVITY REGULATION.
RC STRAIN=ATCC 27294 / TMC 102 / H37Rv;
RX PubMed=10879539; DOI=10.1038/35016103;
RA Stover C.K., Warrener P., VanDevanter D.R., Sherman D.R., Arain T.M.,
RA Langhorne M.H., Anderson S.W., Towell J.A., Yuan Y., McMurray D.N.,
RA Kreiswirth B.N., Barry C.E., Baker W.R.;
RT "A small-molecule nitroimidazopyran drug candidate for the treatment of
RT tuberculosis.";
RL Nature 405:962-966(2000).
RN [4]
RP SUBSTRATE FOR THE TAT PATHWAY, F420-BINDING, SUBCELLULAR LOCATION, AND
RP SUBUNIT.
RC STRAIN=H37Rv;
RX PubMed=23110042; DOI=10.1371/journal.pone.0045003;
RA Bashiri G., Perkowski E.F., Turner A.P., Feltcher M.E., Braunstein M.,
RA Baker E.N.;
RT "Tat-dependent translocation of an F420-binding protein of Mycobacterium
RT tuberculosis.";
RL PLoS ONE 7:E45003-E45003(2012).
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, PATHWAY, AND DRUG
RP TARGET.
RX PubMed=24349169; DOI=10.1371/journal.pone.0081985;
RA Purwantini E., Mukhopadhyay B.;
RT "Rv0132c of Mycobacterium tuberculosis encodes a coenzyme F420-dependent
RT hydroxymycolic acid dehydrogenase.";
RL PLoS ONE 8:E81985-E81985(2013).
CC -!- FUNCTION: Catalyzes the coenzyme F420-dependent oxidation of
CC hydroxymycolic acids (H-MAs) to ketomycolic acids (K-MAs), a lipid
CC class making up the mycobacterial pseudo-outer membrane and over one-
CC third of the dry weight of M.tuberculosis (PubMed:24349169). Does not
CC exhibit F420-dependent glucose-6-phosphate dehydrogenase (FGD) activity
CC (PubMed:23110042). {ECO:0000269|PubMed:23110042,
CC ECO:0000269|PubMed:24349169}.
CC -!- ACTIVITY REGULATION: Is inhibited by the anti-tuberculous drug PA-824,
CC a bicyclic 4-nitroimidazole class compound (PubMed:24349169).
CC Therefore, this is consistent with the finding that PA-824 inhibits the
CC formation of K-MAs and causes an accumulation of hydroxymycolic acids
CC (H-MAs) in M.tuberculosis (PubMed:10879539).
CC {ECO:0000269|PubMed:10879539, ECO:0000269|PubMed:24349169}.
CC -!- PATHWAY: Lipid metabolism; mycolic acid biosynthesis.
CC {ECO:0000269|PubMed:24349169}.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:23110042}.
CC -!- SUBCELLULAR LOCATION: Cell envelope {ECO:0000269|PubMed:23110042}.
CC Note=The Rv0132c-F420 complex is translocated via the Tat pathway
CC across the cytoplasmic membrane, where Rv0132c is anchored to the cell
CC envelope. {ECO:0000269|PubMed:23110042}.
CC -!- PTM: Is exported by the Tat system. The position of the signal peptide
CC cleavage has not been experimentally proven.
CC {ECO:0000269|PubMed:23110042}.
CC -!- PTM: May be lipidated. {ECO:0000305|PubMed:23110042}.
CC -!- SIMILARITY: Belongs to the F420-dependent hydroxymycolic acid
CC dehydrogenase family. {ECO:0000305}.
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DR EMBL; AL123456; CCP42857.1; -; Genomic_DNA.
DR EMBL; CP009480; AIR12853.1; -; Genomic_DNA.
DR RefSeq; NP_214646.1; NC_000962.3.
DR RefSeq; WP_003899826.1; NZ_NVQJ01000001.1.
DR AlphaFoldDB; P96809; -.
DR SMR; P96809; -.
DR STRING; 83332.Rv0132c; -.
DR PaxDb; P96809; -.
DR DNASU; 886877; -.
DR GeneID; 886877; -.
DR KEGG; mtu:Rv0132c; -.
DR PATRIC; fig|83332.111.peg.153; -.
DR TubercuList; Rv0132c; -.
DR eggNOG; COG2141; Bacteria.
DR HOGENOM; CLU_027853_4_0_11; -.
DR OMA; HPWLDNQ; -.
DR PhylomeDB; P96809; -.
DR UniPathway; UPA00915; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0031975; C:envelope; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; HDA:MTBBASE.
DR GO; GO:0016705; F:oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen; IEA:InterPro.
DR GO; GO:0006629; P:lipid metabolic process; IEA:UniProtKB-KW.
DR Gene3D; 3.20.20.30; -; 1.
DR InterPro; IPR031017; F420_FGD2.
DR InterPro; IPR019945; F420_G6P_DH-rel.
DR InterPro; IPR011251; Luciferase-like_dom.
DR InterPro; IPR036661; Luciferase-like_sf.
DR Pfam; PF00296; Bac_luciferase; 1.
DR SUPFAM; SSF51679; SSF51679; 1.
DR TIGRFAMs; TIGR04465; ArgArg_F420; 1.
DR TIGRFAMs; TIGR03557; F420_G6P_family; 1.
PE 1: Evidence at protein level;
KW Lipid biosynthesis; Lipid metabolism; Oxidoreductase; Reference proteome;
KW Signal.
FT SIGNAL 1..40
FT /note="Tat-type signal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00648"
FT CHAIN 41..360
FT /note="F420-dependent hydroxymycolic acid dehydrogenase"
FT /id="PRO_0000435125"
FT ACT_SITE 78
FT /note="Proton donor"
FT /evidence="ECO:0000250|UniProtKB:P9WNE1"
FT ACT_SITE 147
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:P9WNE1"
FT BINDING 77
FT /ligand="coenzyme F420-(gamma-Glu)n"
FT /ligand_id="ChEBI:CHEBI:133980"
FT /evidence="ECO:0000250|UniProtKB:P9WNE1"
FT BINDING 145..146
FT /ligand="coenzyme F420-(gamma-Glu)n"
FT /ligand_id="ChEBI:CHEBI:133980"
FT /evidence="ECO:0000250|UniProtKB:P9WNE1"
FT BINDING 150
FT /ligand="coenzyme F420-(gamma-Glu)n"
FT /ligand_id="ChEBI:CHEBI:133980"
FT /evidence="ECO:0000250|UniProtKB:P9WNE1"
FT BINDING 213..214
FT /ligand="coenzyme F420-(gamma-Glu)n"
FT /ligand_id="ChEBI:CHEBI:133980"
FT /evidence="ECO:0000250|UniProtKB:P9WNE1"
SQ SEQUENCE 360 AA; 38445 MW; C42D1911CB57244A CRC64;
MTGISRRTFG LAAGFGAIGA GGLGGGCSTR SGPTPTPEPA SRGVGVVLSH EQFRTDRLVA
HAQAAEQAGF RYVWASDHLQ PWQDNEGHSM FPWLTLALVG NSTSSILFGT GVTCPIYRYH
PATVAQAFAS LAILNPGRVF LGLGTGERLN EQAATDTFGN YRERHDRLIE AIVLIRQLWS
GERISFTGHY FRTDELKLYD TPAMPPPIFV AASGPQSATL AGRYGDGWIA QARDINDAKL
LAAFAAGAQA AGRDPTTLGK RAELFAVVGD DKAAARAADL WRFTAGAVDQ PNPVEIQRAA
ESNPIEKVLA NWAVGTDPGV HIGAVQAVLD AGAVPFLHFP QDDPITAIDF YRTNVLPELR
