DPRE1_MYCTO
ID DPRE1_MYCTO Reviewed; 461 AA.
AC P9WJF0; L0TDT1; P72056; Q7D4V3;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 41.
DE RecName: Full=Decaprenylphosphoryl-beta-D-ribose oxidase {ECO:0000250|UniProtKB:P9WJF1};
DE EC=1.1.98.3 {ECO:0000250|UniProtKB:P9WJF1};
DE AltName: Full=Decaprenylphospho-beta-D-ribofuranose 2-dehydrogenase {ECO:0000250|UniProtKB:P9WJF1};
DE AltName: Full=Decaprenylphosphoryl-beta-D-ribofuranose 2'-epimerase subunit DprE1 {ECO:0000250|UniProtKB:P9WJF1};
DE Short=Decaprenyl-phosphoribose 2'-epimerase subunit 1 {ECO:0000250|UniProtKB:P9WJF1};
DE AltName: Full=Decaprenylphosphoryl-beta-D-ribofuranose 2'-oxidase {ECO:0000305};
DE AltName: Full=Decaprenylphosphoryl-beta-D-ribose 2-epimerase flavoprotein subunit {ECO:0000250|UniProtKB:P9WJF1};
DE AltName: Full=FAD-dependent decaprenylphosphoryl-beta-D-ribofuranose 2-oxidase {ECO:0000250|UniProtKB:P9WJF1};
GN Name=dprE1 {ECO:0000250|UniProtKB:P9WJF1}; OrderedLocusNames=MT3898;
OS Mycobacterium tuberculosis (strain CDC 1551 / Oshkosh).
OC Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae;
OC Mycobacterium; Mycobacterium tuberculosis complex.
OX NCBI_TaxID=83331;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=CDC 1551 / Oshkosh;
RX PubMed=12218036; DOI=10.1128/jb.184.19.5479-5490.2002;
RA Fleischmann R.D., Alland D., Eisen J.A., Carpenter L., White O.,
RA Peterson J.D., DeBoy R.T., Dodson R.J., Gwinn M.L., Haft D.H., Hickey E.K.,
RA Kolonay J.F., Nelson W.C., Umayam L.A., Ermolaeva M.D., Salzberg S.L.,
RA Delcher A., Utterback T.R., Weidman J.F., Khouri H.M., Gill J., Mikula A.,
RA Bishai W., Jacobs W.R. Jr., Venter J.C., Fraser C.M.;
RT "Whole-genome comparison of Mycobacterium tuberculosis clinical and
RT laboratory strains.";
RL J. Bacteriol. 184:5479-5490(2002).
CC -!- FUNCTION: Component of the DprE1-DprE2 complex that catalyzes the 2-
CC step epimerization of decaprenyl-phospho-ribose (DPR) to decaprenyl-
CC phospho-arabinose (DPA), a key precursor that serves as the arabinose
CC donor required for the synthesis of cell-wall arabinans. DprE1
CC catalyzes the first step of epimerization, namely FAD-dependent
CC oxidation of the C2' hydroxyl of DPR to yield the keto intermediate
CC decaprenyl-phospho-2'-keto-D-arabinose (DPX). The intermediate DPX is
CC then transferred to DprE2 subunit of the epimerase complex, most
CC probably through a 'substrate channel' at the interface of DprE1-DprE2
CC complex. Can also use farnesyl-phosphoryl-beta-D-ribofuranose (FPR) as
CC substrate in vitro. {ECO:0000250|UniProtKB:P9WJF1}.
CC -!- FUNCTION: DprE1 is a highly vulnerable and fully validated tuberculosis
CC drug target. {ECO:0000250|UniProtKB:P9WJF1}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=FAD + H(+) + trans,octa-cis-decaprenylphospho-beta-D-
CC ribofuranose = FADH2 + trans,octa-cis-decaprenylphospho-beta-D-
CC erythro-pentofuranosid-2-ulose; Xref=Rhea:RHEA:33899,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57692, ChEBI:CHEBI:58307,
CC ChEBI:CHEBI:65067, ChEBI:CHEBI:66881; EC=1.1.98.3;
CC Evidence={ECO:0000250|UniProtKB:P9WJF1};
CC -!- ACTIVITY REGULATION: Is inhibited by 8-nitro-benzothiazinones (BTZs)
CC such as BTZ043 and PBTZ169; BTZs are a new class of antimycobacterial
CC agents that kill M.tuberculosis in vitro, ex vivo, and in mouse models
CC of tuberculosis. Is also inhibited by dinitrobenzamide derivatives
CC (DNBs), which thus block formation of both cell-wall lipoarabinomannan
CC and arabinogalactan via inhibition of decaprenyl-phospho-arabinose
CC (DPA) synthesis; DNBs show high activity against intracellular growth
CC of M.tuberculosis inside macrophages, including extensively drug
CC resistant (XDR) strains. BTZs and DNBs are suicide inhibitors that act
CC via covalent modification of DprE1; the essential nitro group of these
CC compounds is reduced by DprE1 to a nitroso group, which then
CC specifically reacts with Cys-387 of DprE1 to form an irreversible
CC semimercaptal adduct. Many other compounds with diverse scaffolds were
CC found to act as either covalent (e.g. nitroquinoxalines,
CC nitroimidazoles) or non-covalent (e.g. the benzothiazole derivative
CC TCA1, the 2-carboxyquinoxaline Ty38C, 8-pyrrole-benzothiazinones, 1,4-
CC azaindoles, pyrazolopyridones, 4-aminoquinolone piperidine amides)
CC DprE1 inhibitors. {ECO:0000250|UniProtKB:P9WJF1}.
CC -!- PATHWAY: Cell wall biogenesis; cell wall polysaccharide biosynthesis.
CC {ECO:0000250|UniProtKB:P9WJF1}.
CC -!- SUBUNIT: Monomer. Although forming apparent dimer in crystals, DprE1
CC does not dimerize appreciably in solution. Interacts with DprE2 to form
CC an epimerase complex. {ECO:0000250|UniProtKB:P9WJF1}.
CC -!- SUBCELLULAR LOCATION: Periplasm {ECO:0000250|UniProtKB:P9WJF1}.
CC -!- SIMILARITY: Belongs to the DprE1 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAK48263.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AE000516; AAK48263.1; ALT_INIT; Genomic_DNA.
DR PIR; B70697; B70697.
DR RefSeq; WP_003420630.1; NZ_KK341227.1.
DR AlphaFoldDB; P9WJF0; -.
DR SMR; P9WJF0; -.
DR PRIDE; P9WJF0; -.
DR EnsemblBacteria; AAK48263; AAK48263; MT3898.
DR KEGG; mtc:MT3898; -.
DR PATRIC; fig|83331.31.peg.4194; -.
DR HOGENOM; CLU_032465_0_0_11; -.
DR BRENDA; 1.1.98.3; 3445.
DR UniPathway; UPA00963; -.
DR Proteomes; UP000001020; Chromosome.
DR GO; GO:0016020; C:membrane; IEA:InterPro.
DR GO; GO:0042597; C:periplasmic space; IEA:UniProtKB-SubCell.
DR GO; GO:0003885; F:D-arabinono-1,4-lactone oxidase activity; IEA:InterPro.
DR GO; GO:0071949; F:FAD binding; IEA:InterPro.
DR GO; GO:0045227; P:capsule polysaccharide biosynthetic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0071555; P:cell wall organization; IEA:UniProtKB-KW.
DR GO; GO:0046677; P:response to antibiotic; IEA:UniProtKB-KW.
DR Gene3D; 3.30.465.10; -; 1.
DR InterPro; IPR007173; ALO_C.
DR InterPro; IPR016166; FAD-bd_PCMH.
DR InterPro; IPR036318; FAD-bd_PCMH-like_sf.
DR InterPro; IPR016169; FAD-bd_PCMH_sub2.
DR InterPro; IPR006094; Oxid_FAD_bind_N.
DR Pfam; PF04030; ALO; 1.
DR Pfam; PF01565; FAD_binding_4; 1.
DR SUPFAM; SSF56176; SSF56176; 1.
DR PROSITE; PS51387; FAD_PCMH; 1.
PE 3: Inferred from homology;
KW Antibiotic resistance; Cell wall biogenesis/degradation; FAD; Flavoprotein;
KW Oxidoreductase; Periplasm.
FT CHAIN 1..461
FT /note="Decaprenylphosphoryl-beta-D-ribose oxidase"
FT /id="PRO_0000427841"
FT DOMAIN 19..194
FT /note="FAD-binding PCMH-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00718"
FT BINDING 53..63
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:P9WJF1"
FT BINDING 117
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:P9WJF1"
FT BINDING 122..125
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:P9WJF1"
FT BINDING 129..132
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:P9WJF1"
FT BINDING 184
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:P9WJF1"
FT BINDING 415
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:P9WJF1"
SQ SEQUENCE 461 AA; 50163 MW; B9B770002E5FE81C CRC64;
MLSVGATTTA TRLTGWGRTA PSVANVLRTP DAEMIVKAVA RVAESGGGRG AIARGLGRSY
GDNAQNGGGL VIDMTPLNTI HSIDADTKLV DIDAGVNLDQ LMKAALPFGL WVPVLPGTRQ
VTVGGAIACD IHGKNHHSAG SFGNHVRSMD LLTADGEIRH LTPTGEDAEL FWATVGGNGL
TGIIMRATIE MTPTSTAYFI ADGDVTASLD ETIALHSDGS EARYTYSSAW FDAISAPPKL
GRAAVSRGRL ATVEQLPAKL RSEPLKFDAP QLLTLPDVFP NGLANKYTFG PIGELWYRKS
GTYRGKVQNL TQFYHPLDMF GEWNRAYGPA GFLQYQFVIP TEAVDEFKKI IGVIQASGHY
SFLNVFKLFG PRNQAPLSFP IPGWNICVDF PIKDGLGKFV SELDRRVLEF GGRLYTAKDS
RTTAETFHAM YPRVDEWISV RRKVDPLRVF ASDMARRLEL L
