NFNB_MYCS2
ID NFNB_MYCS2 Reviewed; 234 AA.
AC A0R6D0; I7GGH9;
DT 16-SEP-2015, integrated into UniProtKB/Swiss-Prot.
DT 09-JAN-2007, sequence version 1.
DT 03-AUG-2022, entry version 94.
DE RecName: Full=Nitroreductase NfnB {ECO:0000303|PubMed:20624223, ECO:0000312|EMBL:ABK74228.1, ECO:0000312|EMBL:AFP42759.1};
DE Short=NR NfnB {ECO:0000303|PubMed:20624223};
DE EC=1.-.-.- {ECO:0000269|PubMed:20624223, ECO:0000269|PubMed:22069462};
DE AltName: Full=FMN-dependent NAD(P)H nitroreductase {ECO:0000303|PubMed:20624223};
GN Name=nfnB {ECO:0000303|PubMed:20624223, ECO:0000303|PubMed:22069462};
GN OrderedLocusNames=MSMEG_6505 {ECO:0000312|EMBL:ABK74228.1},
GN MSMEI_6333 {ECO:0000312|EMBL:AFP42759.1};
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] {ECO:0000312|EMBL:ABK74228.1, ECO:0000312|Proteomes:UP000000757}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 700084 / mc(2)155 {ECO:0000312|Proteomes:UP000000757};
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] {ECO:0000312|EMBL:AFP42759.1, ECO:0000312|Proteomes:UP000006158}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 700084 / mc(2)155 {ECO:0000312|Proteomes:UP000006158};
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] {ECO:0000312|EMBL:AFP42759.1, ECO:0000312|Proteomes:UP000006158}
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 FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=22069462; DOI=10.1371/journal.pone.0026675;
RA Ribeiro A.L., Degiacomi G., Ewann F., Buroni S., Incandela M.L.,
RA Chiarelli L.R., Mori G., Kim J., Contreras-Dominguez M., Park Y.S.,
RA Han S.J., Brodin P., Valentini G., Rizzi M., Riccardi G., Pasca M.R.;
RT "Analogous mechanisms of resistance to benzothiazinones and
RT dinitrobenzamides in Mycobacterium smegmatis.";
RL PLoS ONE 6:E26675-E26675(2011).
RN [5] {ECO:0007744|PDB:2WZV, ECO:0007744|PDB:2WZW}
RP X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) IN COMPLEX WITH FMN AND NADP,
RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, BIOPHYSICOCHEMICAL PROPERTIES,
RP SUBUNIT, INDUCTION, DISRUPTION PHENOTYPE, AND BIOTECHNOLOGY.
RC STRAIN=ATCC 700084 / mc(2)155 {ECO:0000303|PubMed:20624223};
RX PubMed=20624223; DOI=10.1111/j.1365-2958.2010.07277.x;
RA Manina G., Bellinzoni M., Pasca M.R., Neres J., Milano A., Ribeiro A.L.,
RA Buroni S., Skovierova H., Dianiskova P., Mikusova K., Marak J., Makarov V.,
RA Giganti D., Haouz A., Lucarelli A.P., Degiacomi G., Piazza A.,
RA Chiarelli L.R., De Rossi E., Salina E., Cole S.T., Alzari P.M.,
RA Riccardi G.;
RT "Biological and structural characterization of the Mycobacterium smegmatis
RT nitroreductase NfnB, and its role in benzothiazinone resistance.";
RL Mol. Microbiol. 77:1172-1185(2010).
CC -!- FUNCTION: Confers resistance to antitubercular drugs benzothiazinone
CC (BTZ) and dinitrobenzamide (DNB). Inactivates BTZ and DNB by reducing
CC an essential nitro group of these compounds to amino group or to
CC hydroxyl amine, respectively, using NADH or NADPH as source of reducing
CC equivalents; two electrons are transferred (PubMed:22069462,
CC PubMed:20624223). Able to reduce the nitro group of bicyclic
CC nitroimidazole PA-824, but not of quinone menadione, nitrofurazone,
CC methyl-4-nitrobenzoate, 4-nitrobenzene methyl sulfonate or 4-
CC nitroacetophenone (PubMed:20624223). {ECO:0000269|PubMed:20624223,
CC ECO:0000269|PubMed:22069462}.
CC -!- COFACTOR:
CC Name=FMN; Xref=ChEBI:CHEBI:58210;
CC Evidence={ECO:0000269|PubMed:20624223};
CC Note=Binds 1 FMN per subunit. {ECO:0000269|PubMed:20624223};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=10.75 uM for NADH (at pH 8.0 and 25 degrees Celsius)
CC {ECO:0000269|PubMed:20624223};
CC KM=8.15 uM for NADPH (at pH 8.0 and 25 degrees Celsius)
CC {ECO:0000269|PubMed:20624223};
CC pH dependence:
CC Optimum pH is 7.5 to 9.0. {ECO:0000269|PubMed:20624223};
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:20624223}.
CC -!- INDUCTION: Transcriptionally repressed by MSMEG_6503/MSMEI_6332.
CC {ECO:0000269|PubMed:20624223}.
CC -!- DISRUPTION PHENOTYPE: Loss of resistance to antitubercular drug BTZ043,
CC but still resistant to PA-824. {ECO:0000269|PubMed:20624223}.
CC -!- BIOTECHNOLOGY: Potentially helps in the design of second generation BTZ
CC and DNB drugs that are less susceptible to nitroreduction.
CC {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the nitroreductase family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AFP42759.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; CP000480; ABK74228.1; -; Genomic_DNA.
DR EMBL; CP001663; AFP42759.1; ALT_INIT; Genomic_DNA.
DR RefSeq; WP_011731326.1; NC_018289.1.
DR RefSeq; YP_890718.1; NC_008596.1.
DR PDB; 2WZV; X-ray; 1.75 A; A/B=1-234.
DR PDB; 2WZW; X-ray; 1.80 A; A/B=1-234.
DR PDBsum; 2WZV; -.
DR PDBsum; 2WZW; -.
DR AlphaFoldDB; A0R6D0; -.
DR SMR; A0R6D0; -.
DR STRING; 246196.MSMEI_6333; -.
DR EnsemblBacteria; ABK74228; ABK74228; MSMEG_6505.
DR EnsemblBacteria; AFP42759; AFP42759; MSMEI_6333.
DR KEGG; msg:MSMEI_6333; -.
DR KEGG; msm:MSMEG_6505; -.
DR PATRIC; fig|246196.19.peg.6329; -.
DR eggNOG; COG0778; Bacteria.
DR OMA; MRGFRQF; -.
DR EvolutionaryTrace; A0R6D0; -.
DR Proteomes; UP000000757; Chromosome.
DR Proteomes; UP000006158; Chromosome.
DR GO; GO:0010181; F:FMN binding; IDA:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IDA:UniProtKB.
DR GO; GO:0050661; F:NADP binding; IDA:UniProtKB.
DR GO; GO:0016491; F:oxidoreductase activity; IDA:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR GO; GO:0042178; P:xenobiotic catabolic process; IDA:UniProtKB.
DR Gene3D; 3.40.109.10; -; 1.
DR InterPro; IPR029479; Nitroreductase.
DR InterPro; IPR000415; Nitroreductase-like.
DR Pfam; PF00881; Nitroreductase; 1.
DR SUPFAM; SSF55469; SSF55469; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Flavoprotein; FMN; NAD; NADP; Nucleotide-binding;
KW Oxidoreductase; Reference proteome.
FT CHAIN 1..234
FT /note="Nitroreductase NfnB"
FT /id="PRO_0000433873"
FT BINDING 25..29
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000269|PubMed:20624223,
FT ECO:0007744|PDB:2WZV, ECO:0007744|PDB:2WZW"
FT BINDING 55
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:20624223,
FT ECO:0007744|PDB:2WZW"
FT BINDING 105
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:20624223,
FT ECO:0007744|PDB:2WZW"
FT BINDING 113
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:20624223,
FT ECO:0007744|PDB:2WZW"
FT BINDING 118
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:20624223"
FT BINDING 137
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000269|PubMed:20624223,
FT ECO:0007744|PDB:2WZV, ECO:0007744|PDB:2WZW"
FT BINDING 181..182
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000269|PubMed:20624223,
FT ECO:0007744|PDB:2WZV, ECO:0007744|PDB:2WZW"
FT BINDING 223
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000269|PubMed:20624223,
FT ECO:0007744|PDB:2WZV, ECO:0007744|PDB:2WZW"
FT HELIX 14..24
FT /evidence="ECO:0007829|PDB:2WZV"
FT HELIX 38..48
FT /evidence="ECO:0007829|PDB:2WZV"
FT HELIX 54..56
FT /evidence="ECO:0007829|PDB:2WZV"
FT STRAND 61..65
FT /evidence="ECO:0007829|PDB:2WZV"
FT HELIX 67..82
FT /evidence="ECO:0007829|PDB:2WZV"
FT HELIX 99..116
FT /evidence="ECO:0007829|PDB:2WZV"
FT HELIX 123..134
FT /evidence="ECO:0007829|PDB:2WZV"
FT HELIX 135..138
FT /evidence="ECO:0007829|PDB:2WZV"
FT STRAND 140..148
FT /evidence="ECO:0007829|PDB:2WZV"
FT HELIX 153..172
FT /evidence="ECO:0007829|PDB:2WZV"
FT STRAND 176..180
FT /evidence="ECO:0007829|PDB:2WZV"
FT HELIX 181..185
FT /evidence="ECO:0007829|PDB:2WZV"
FT HELIX 187..194
FT /evidence="ECO:0007829|PDB:2WZV"
FT STRAND 198..208
FT /evidence="ECO:0007829|PDB:2WZV"
FT HELIX 215..218
FT /evidence="ECO:0007829|PDB:2WZV"
FT HELIX 226..229
FT /evidence="ECO:0007829|PDB:2WZV"
FT STRAND 230..233
FT /evidence="ECO:0007829|PDB:2WZV"
SQ SEQUENCE 234 AA; 25525 MW; B41249FB9F4AD53D CRC64;
MSVPTLPTGP TVDLAQAAER LIKGRRAVRA FRPDEVPEET MRAVFELAGH APSNSNTQPW
HVEVVSGAAR DRLAEALVTA HAEERVTVDF PYREGLFQGV LQERRADFGS RLYAALGIAR
DQTDLLQGYN TESLRFYGAP HVAMLFAPNN TEARIAGDMG IYAQTLMLAM TAHGIASCPQ
ALLSFYADTV RAELGVENRK LLMGISFGYA DDTAAVNGVR IPRAGLSETT RFSR
