DPRE1_MYCS2
ID DPRE1_MYCS2 Reviewed; 460 AA.
AC A0R607; I7FMU1;
DT 01-APR-2015, integrated into UniProtKB/Swiss-Prot.
DT 01-APR-2015, sequence version 2.
DT 03-AUG-2022, entry version 105.
DE RecName: Full=Decaprenylphosphoryl-beta-D-ribose oxidase {ECO:0000305};
DE EC=1.1.98.3 {ECO:0000269|PubMed:22188377};
DE AltName: Full=Decaprenylphospho-beta-D-ribofuranose 2-dehydrogenase {ECO:0000305|PubMed:22956199};
DE AltName: Full=Decaprenylphosphoryl-beta-D-ribofuranose 2'-epimerase subunit DprE1 {ECO:0000305|PubMed:22188377};
DE Short=Decaprenyl-phosphoribose 2'-epimerase subunit 1 {ECO:0000305|PubMed:22188377};
DE AltName: Full=Decaprenylphosphoryl-beta-D-ribofuranose 2'-oxidase {ECO:0000303|PubMed:22188377};
DE AltName: Full=Decaprenylphosphoryl-beta-D-ribose 2-epimerase flavoprotein subunit {ECO:0000305};
DE AltName: Full=FAD-dependent decaprenylphosphoryl-beta-D-ribofuranose 2-oxidase {ECO:0000305|PubMed:22188377};
GN Name=dprE1 {ECO:0000303|PubMed:22188377};
GN OrderedLocusNames=MSMEG_6382, MSMEI_6214; ORFNames=LJ00_31545;
OS Mycolicibacterium smegmatis (strain ATCC 700084 / mc(2)155) (Mycobacterium
OS smegmatis).
OC Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae;
OC Mycolicibacterium.
OX NCBI_TaxID=246196;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 700084 / mc(2)155;
RA Fleischmann R.D., Dodson R.J., Haft D.H., Merkel J.S., Nelson W.C.,
RA Fraser C.M.;
RL Submitted (OCT-2006) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 700084 / mc(2)155;
RX PubMed=17295914; DOI=10.1186/gb-2007-8-2-r20;
RA Deshayes C., Perrodou E., Gallien S., Euphrasie D., Schaeffer C.,
RA Van-Dorsselaer A., Poch O., Lecompte O., Reyrat J.-M.;
RT "Interrupted coding sequences in Mycobacterium smegmatis: authentic
RT mutations or sequencing errors?";
RL Genome Biol. 8:R20.1-R20.9(2007).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 700084 / mc(2)155;
RX PubMed=18955433; DOI=10.1101/gr.081901.108;
RA Gallien S., Perrodou E., Carapito C., Deshayes C., Reyrat J.-M.,
RA Van Dorsselaer A., Poch O., Schaeffer C., Lecompte O.;
RT "Ortho-proteogenomics: multiple proteomes investigation through orthology
RT and a new MS-based protocol.";
RL Genome Res. 19:128-135(2009).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 700084 / mc(2)155;
RX PubMed=25657281; DOI=10.1128/genomea.01520-14;
RA Mohan A., Padiadpu J., Baloni P., Chandra N.;
RT "Complete genome sequences of a Mycobacterium smegmatis laboratory strain
RT (MC2 155) and isoniazid-resistant (4XR1/R2) mutant strains.";
RL Genome Announc. 3:E01520-E01520(2015).
RN [5]
RP ACTIVITY REGULATION, DRUG TARGET, AND BTZ043-RESISTANT VARIANTS MN47 AND
RP MN84.
RC STRAIN=ATCC 700084 / mc(2)155;
RX PubMed=19299584; DOI=10.1126/science.1171583;
RA Makarov V., Manina G., Mikusova K., Mollmann U., Ryabova O.,
RA Saint-Joanis B., Dhar N., Pasca M.R., Buroni S., Lucarelli A.P., Milano A.,
RA De Rossi E., Belanova M., Bobovska A., Dianiskova P., Kordulakova J.,
RA Sala C., Fullam E., Schneider P., McKinney J.D., Brodin P., Christophe T.,
RA Waddell S., Butcher P., Albrethsen J., Rosenkrands I., Brosch R., Nandi V.,
RA Bharath S., Gaonkar S., Shandil R.K., Balasubramanian V., Balganesh T.,
RA Tyagi S., Grosset J., Riccardi G., Cole S.T.;
RT "Benzothiazinones kill Mycobacterium tuberculosis by blocking arabinan
RT synthesis.";
RL Science 324:801-804(2009).
RN [6]
RP DISRUPTION PHENOTYPE, AND PATHWAY.
RC STRAIN=ATCC 700084 / mc(2)155;
RX PubMed=21346818; DOI=10.1371/journal.pone.0016869;
RA Crellin P.K., Brammananth R., Coppel R.L.;
RT "Decaprenylphosphoryl-beta-D-ribose 2'-epimerase, the target of
RT benzothiazinones and dinitrobenzamides, is an essential enzyme in
RT Mycobacterium smegmatis.";
RL PLoS ONE 6:E16869-E16869(2011).
RN [7]
RP FUNCTION, CATALYTIC ACTIVITY, MUTAGENESIS OF CYS-386, ACTIVITY REGULATION,
RP AND SUBSTRATE SPECIFICITY.
RC STRAIN=ATCC 700084 / mc(2)155;
RX PubMed=22188377; DOI=10.1021/ja211042r;
RA Trefzer C., Skovierova H., Buroni S., Bobovska A., Nenci S., Molteni E.,
RA Pojer F., Pasca M.R., Makarov V., Cole S.T., Riccardi G., Mikusova K.,
RA Johnsson K.;
RT "Benzothiazinones are suicide inhibitors of mycobacterial
RT decaprenylphosphoryl-beta-D-ribofuranose 2'-oxidase DprE1.";
RL J. Am. Chem. Soc. 134:912-915(2012).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) IN COMPLEXES WITH FAD AND THE
RP BENZOTHIAZINONE BTZ043 INHIBITOR, FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES,
RP MUTAGENESIS OF GLN-335; CYS-386 AND LYS-417, ACTIVITY REGULATION, AND
RP SUBUNIT.
RC STRAIN=ATCC 700084 / mc(2)155;
RX PubMed=22956199; DOI=10.1126/scitranslmed.3004395;
RA Neres J., Pojer F., Molteni E., Chiarelli L.R., Dhar N., Boy-Rottger S.,
RA Buroni S., Fullam E., Degiacomi G., Lucarelli A.P., Read R.J., Zanoni G.,
RA Edmondson D.E., De Rossi E., Pasca M.R., McKinney J.D., Dyson P.J.,
RA Riccardi G., Mattevi A., Cole S.T., Binda C.;
RT "Structural basis for benzothiazinone-mediated killing of Mycobacterium
RT tuberculosis.";
RL Sci. Transl. Med. 4:150RA121-150RA121(2012).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (2.35 ANGSTROMS) OF 58-460.
RC STRAIN=ATCC 607 / DSM 43465 / JCM 20379 / NBRC 3207 / NRRL B-692;
RX PubMed=23184707; DOI=10.1002/prot.24220;
RA Li H., Jogl G.;
RT "Crystal structure of decaprenylphosphoryl-beta- D-ribose 2'-epimerase from
RT Mycobacterium smegmatis.";
RL Proteins 81:538-543(2013).
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
CC (PubMed:22188377). DprE1 catalyzes the first step of epimerization,
CC namely FAD-dependent oxidation of the C2' hydroxyl of DPR to yield the
CC keto intermediate decaprenyl-phospho-2'-keto-D-arabinose (DPX)
CC (PubMed:22188377). The intermediate DPX is then transferred to DprE2
CC subunit of the epimerase complex, most probably through a 'substrate
CC channel' at the interface of DprE1-DprE2 complex (By similarity). Can
CC also use farnesyl-phosphoryl-beta-D-ribofuranose (FPR) as substrate in
CC vitro (PubMed:22188377, PubMed:22956199). Appears to be essential for
CC the growth of M.smegmatis (PubMed:21346818).
CC {ECO:0000250|UniProtKB:P9WJF1, ECO:0000269|PubMed:21346818,
CC ECO:0000269|PubMed:22188377, ECO:0000269|PubMed:22956199}.
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:0000269|PubMed:22188377};
CC -!- ACTIVITY REGULATION: Is inhibited by 8-nitro-benzothiazinones (BTZs)
CC such as BTZ043; BTZs are a new class of antimycobacterial agents that
CC block formation of both cell-wall lipoarabinomannan and arabinogalactan
CC via inhibition of decaprenyl-phospho-arabinose (DPA) synthesis
CC (PubMed:19299584, PubMed:22188377). BTZs are suicide inhibitors that
CC act via covalent modification of DprE1; the essential nitro group of
CC these compounds is reduced by DprE1 to a nitroso group, which then
CC specifically reacts with Cys-386 of DprE1 to form an irreversible
CC semimercaptal adduct (PubMed:22188377, PubMed:22956199). Other
CC compounds with diverse scaffolds (dinitrobenzamides and
CC nitrobenzoquinoxalines) also act as covalent DprE1 inhibitors
CC (PubMed:22956199). {ECO:0000269|PubMed:19299584,
CC ECO:0000269|PubMed:22188377, ECO:0000269|PubMed:22956199}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.11 mM for FPR (at pH 8.5 and 25 degrees Celsius)
CC {ECO:0000269|PubMed:22956199};
CC Note=kcat is 12.7 min(-1) for epimerase activity with FPR as
CC substrate (at pH 8.5 and 25 degrees Celsius).
CC {ECO:0000269|PubMed:22956199};
CC -!- PATHWAY: Cell wall biogenesis; cell wall polysaccharide biosynthesis.
CC {ECO:0000305|PubMed:21346818}.
CC -!- SUBUNIT: Monomer (PubMed:22956199). Interacts with DprE2 to form an
CC epimerase complex (By similarity). {ECO:0000250|UniProtKB:P9WJF1,
CC ECO:0000269|PubMed:22956199}.
CC -!- SUBCELLULAR LOCATION: Periplasm {ECO:0000250|UniProtKB:P9WJF1}.
CC -!- DISRUPTION PHENOTYPE: Disruption of this gene is only possible in the
CC presence of a plasmid-encoded copy of the gene. Curing of this 'rescue'
CC plasmid from the bacterial population results in a cessation of growth,
CC demonstrating gene essentiality. {ECO:0000269|PubMed:21346818}.
CC -!- SIMILARITY: Belongs to the DprE1 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=ABK72795.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; CP000480; ABK72795.1; ALT_INIT; Genomic_DNA.
DR EMBL; CP001663; AFP42640.1; -; Genomic_DNA.
DR EMBL; CP009494; AIU11363.1; -; Genomic_DNA.
DR RefSeq; WP_003897792.1; NZ_SIJM01000013.1.
DR RefSeq; YP_890595.1; NC_008596.1.
DR PDB; 4AUT; X-ray; 2.10 A; A=1-460.
DR PDB; 4F4Q; X-ray; 2.62 A; A=1-460.
DR PDB; 4G3T; X-ray; 2.35 A; A=58-460.
DR PDB; 4G3U; X-ray; 2.69 A; A/B=58-460.
DR PDBsum; 4AUT; -.
DR PDBsum; 4F4Q; -.
DR PDBsum; 4G3T; -.
DR PDBsum; 4G3U; -.
DR AlphaFoldDB; A0R607; -.
DR SMR; A0R607; -.
DR STRING; 246196.MSMEI_6214; -.
DR ChEMBL; CHEMBL3797019; -.
DR PRIDE; A0R607; -.
DR EnsemblBacteria; ABK72795; ABK72795; MSMEG_6382.
DR EnsemblBacteria; AFP42640; AFP42640; MSMEI_6214.
DR GeneID; 66737660; -.
DR KEGG; msb:LJ00_31545; -.
DR KEGG; msg:MSMEI_6214; -.
DR KEGG; msm:MSMEG_6382; -.
DR PATRIC; fig|246196.19.peg.6209; -.
DR eggNOG; COG0277; Bacteria.
DR HOGENOM; CLU_032465_0_0_11; -.
DR BioCyc; MetaCyc:MON-17534; -.
DR BRENDA; 1.1.98.3; 3512.
DR UniPathway; UPA00963; -.
DR Proteomes; UP000000757; Chromosome.
DR Proteomes; UP000006158; 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; 1.10.45.10; -; 1.
DR Gene3D; 3.30.43.10; -; 1.
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; IPR016167; FAD-bd_PCMH_sub1.
DR InterPro; IPR016169; FAD-bd_PCMH_sub2.
DR InterPro; IPR006094; Oxid_FAD_bind_N.
DR InterPro; IPR016171; Vanillyl_alc_oxidase_C-sub2.
DR Pfam; PF04030; ALO; 1.
DR Pfam; PF01565; FAD_binding_4; 1.
DR SUPFAM; SSF56176; SSF56176; 1.
DR PROSITE; PS51387; FAD_PCMH; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Antibiotic resistance; Cell wall biogenesis/degradation; FAD;
KW Flavoprotein; Nucleotide-binding; Oxidoreductase; Periplasm;
KW Reference proteome.
FT CHAIN 1..460
FT /note="Decaprenylphosphoryl-beta-D-ribose oxidase"
FT /id="PRO_0000432471"
FT DOMAIN 19..193
FT /note="FAD-binding PCMH-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00718"
FT BINDING 52..62
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:22956199,
FT ECO:0007744|PDB:4AUT, ECO:0007744|PDB:4F4Q"
FT BINDING 116
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:22956199,
FT ECO:0007744|PDB:4AUT, ECO:0007744|PDB:4F4Q"
FT BINDING 121..124
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:22956199,
FT ECO:0007744|PDB:4AUT, ECO:0007744|PDB:4F4Q"
FT BINDING 128..131
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:22956199,
FT ECO:0007744|PDB:4AUT, ECO:0007744|PDB:4F4Q"
FT BINDING 183
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:22956199,
FT ECO:0007744|PDB:4AUT, ECO:0007744|PDB:4F4Q"
FT BINDING 414
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:22956199,
FT ECO:0007744|PDB:4AUT, ECO:0007744|PDB:4F4Q"
FT VARIANT 386
FT /note="C -> G (in strain: MN47; BTZ043-resistant)"
FT /evidence="ECO:0000269|PubMed:19299584"
FT VARIANT 386
FT /note="C -> S (in strain: MN84; BTZ043-resistant)"
FT /evidence="ECO:0000269|PubMed:19299584"
FT MUTAGEN 335
FT /note="Q->A: 10-fold decrease in catalytic efficiency."
FT /evidence="ECO:0000269|PubMed:22956199"
FT MUTAGEN 386
FT /note="C->G: 14-fold decrease in catalytic efficiency.
FT Reduces BTZs to inert metabolites while avoiding covalent
FT inactivation."
FT /evidence="ECO:0000269|PubMed:22188377,
FT ECO:0000269|PubMed:22956199"
FT MUTAGEN 417
FT /note="K->A: Loss of catalytic activity."
FT /evidence="ECO:0000269|PubMed:22956199"
FT STRAND 8..13
FT /evidence="ECO:0007829|PDB:4AUT"
FT STRAND 22..27
FT /evidence="ECO:0007829|PDB:4AUT"
FT HELIX 32..40
FT /evidence="ECO:0007829|PDB:4AUT"
FT HELIX 42..45
FT /evidence="ECO:0007829|PDB:4AUT"
FT STRAND 50..55
FT /evidence="ECO:0007829|PDB:4AUT"
FT STRAND 58..61
FT /evidence="ECO:0007829|PDB:4AUT"
FT STRAND 68..72
FT /evidence="ECO:0007829|PDB:4AUT"
FT HELIX 73..75
FT /evidence="ECO:0007829|PDB:4AUT"
FT STRAND 79..83
FT /evidence="ECO:0007829|PDB:4AUT"
FT TURN 84..87
FT /evidence="ECO:0007829|PDB:4AUT"
FT STRAND 88..92
FT /evidence="ECO:0007829|PDB:4AUT"
FT HELIX 97..104
FT /evidence="ECO:0007829|PDB:4AUT"
FT HELIX 105..107
FT /evidence="ECO:0007829|PDB:4AUT"
FT HELIX 122..127
FT /evidence="ECO:0007829|PDB:4AUT"
FT HELIX 135..138
FT /evidence="ECO:0007829|PDB:4AUT"
FT HELIX 141..144
FT /evidence="ECO:0007829|PDB:4AUT"
FT STRAND 145..151
FT /evidence="ECO:0007829|PDB:4AUT"
FT STRAND 157..160
FT /evidence="ECO:0007829|PDB:4AUT"
FT STRAND 162..164
FT /evidence="ECO:0007829|PDB:4AUT"
FT HELIX 167..173
FT /evidence="ECO:0007829|PDB:4AUT"
FT TURN 177..180
FT /evidence="ECO:0007829|PDB:4AUT"
FT STRAND 182..189
FT /evidence="ECO:0007829|PDB:4AUT"
FT STRAND 196..204
FT /evidence="ECO:0007829|PDB:4AUT"
FT HELIX 208..216
FT /evidence="ECO:0007829|PDB:4AUT"
FT HELIX 219..222
FT /evidence="ECO:0007829|PDB:4AUT"
FT STRAND 224..230
FT /evidence="ECO:0007829|PDB:4AUT"
FT STRAND 232..234
FT /evidence="ECO:0007829|PDB:4G3T"
FT TURN 236..240
FT /evidence="ECO:0007829|PDB:4AUT"
FT STRAND 242..249
FT /evidence="ECO:0007829|PDB:4AUT"
FT HELIX 252..254
FT /evidence="ECO:0007829|PDB:4AUT"
FT HELIX 257..261
FT /evidence="ECO:0007829|PDB:4AUT"
FT STRAND 302..308
FT /evidence="ECO:0007829|PDB:4AUT"
FT HELIX 309..313
FT /evidence="ECO:0007829|PDB:4AUT"
FT TURN 314..317
FT /evidence="ECO:0007829|PDB:4AUT"
FT STRAND 331..339
FT /evidence="ECO:0007829|PDB:4AUT"
FT HELIX 343..356
FT /evidence="ECO:0007829|PDB:4AUT"
FT STRAND 361..368
FT /evidence="ECO:0007829|PDB:4AUT"
FT STRAND 381..390
FT /evidence="ECO:0007829|PDB:4AUT"
FT HELIX 395..408
FT /evidence="ECO:0007829|PDB:4AUT"
FT HELIX 415..417
FT /evidence="ECO:0007829|PDB:4AUT"
FT HELIX 423..429
FT /evidence="ECO:0007829|PDB:4AUT"
FT HELIX 433..443
FT /evidence="ECO:0007829|PDB:4AUT"
FT HELIX 452..456
FT /evidence="ECO:0007829|PDB:4AUT"
SQ SEQUENCE 460 AA; 50377 MW; 2F19107D18638FC0 CRC64;
MSTTEFPTTT KRLMGWGRTA PTVASVLSTS DPEVIVRAVT RAAEEGGRGV IARGLGRSYG
DNAQNGGGLV IDMPALNRIH SIDSGTRLVD VDAGVSLDQL MKAALPHGLW VPVLPGTRQV
TVGGAIGCDI HGKNHHSAGS FGNHVRSMEL LTANGEVRHL TPAGPDSDLF WATVGGNGLT
GIILRATIEM TPTETAYFIA DGDVTGSLDE TIAFHSDGSE ANYTYSSAWF DAISKPPKLG
RAAISRGSLA KLDQLPSKLQ KDPLKFDAPQ LLTLPDIFPN GLANKFTFMP IGELWYRKSG
TYRNKVQNLT QFYHPLDMFG EWNRAYGSAG FLQYQFVVPT EAVEEFKSII VDIQRSGHYS
FLNVFKLFGP GNQAPLSFPI PGWNVCVDFP IKAGLHEFVT ELDRRVLEFG GRLYTAKDSR
TTAETFHAMY PRIDEWIRIR RSVDPDGVFA SDMARRLQLL
