RPFB_MYCTU
ID RPFB_MYCTU Reviewed; 362 AA.
AC P9WG29; F2GHD1; L0T719; O05594; Q7D900;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 25-MAY-2022, entry version 41.
DE RecName: Full=Resuscitation-promoting factor RpfB;
DE EC=3.-.-.-;
DE Flags: Precursor;
GN Name=rpfB; OrderedLocusNames=Rv1009; ORFNames=MTC1237.26;
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 FUNCTION, AND INDUCTION.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=12410821; DOI=10.1046/j.1365-2958.2002.03184.x;
RA Mukamolova G.V., Turapov O.A., Young D.I., Kaprelyants A.S., Kell D.B.,
RA Young M.;
RT "A family of autocrine growth factors in Mycobacterium tuberculosis.";
RL Mol. Microbiol. 46:623-635(2002).
RN [3]
RP BIOTECHNOLOGY.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=12874362; DOI=10.1128/iai.71.8.4789-4794.2003;
RA Yeremeev V.V., Kondratieva T.K., Rubakova E.I., Petrovskaya S.N.,
RA Kazarian K.A., Telkov M.V., Biketov S.F., Kaprelyants A.S., Apt A.S.;
RT "Proteins of the Rpf family: immune cell reactivity and vaccination
RT efficacy against tuberculosis in mice.";
RL Infect. Immun. 71:4789-4794(2003).
RN [4]
RP FUNCTION.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=12906837; DOI=10.1016/s1472-9792(03)00052-0;
RA Zhu W., Plikaytis B.B., Shinnick T.M.;
RT "Resuscitation factors from mycobacteria: homologs of Micrococcus luteus
RT proteins.";
RL Tuberculosis 83:261-269(2003).
RN [5]
RP DISRUPTION PHENOTYPE.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=15207486; DOI=10.1016/j.tube.2003.12.004;
RA Downing K.J., Betts J.C., Young D.I., McAdam R.A., Kelly F., Young M.,
RA Mizrahi V.;
RT "Global expression profiling of strains harbouring null mutations reveals
RT that the five rpf-like genes of Mycobacterium tuberculosis show functional
RT redundancy.";
RL Tuberculosis 84:167-179(2004).
RN [6]
RP INTERACTION WITH RIPA, AND SUBCELLULAR LOCATION.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=17919286; DOI=10.1111/j.1365-2958.2007.05945.x;
RA Hett E.C., Chao M.C., Steyn A.J., Fortune S.M., Deng L.L., Rubin E.J.;
RT "A partner for the resuscitation-promoting factors of Mycobacterium
RT tuberculosis.";
RL Mol. Microbiol. 66:658-668(2007).
RN [7]
RP DISRUPTION PHENOTYPE.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=18186793; DOI=10.1111/j.1365-2958.2007.06078.x;
RA Kana B.D., Gordhan B.G., Downing K.J., Sung N., Vostroktunova G.,
RA Machowski E.E., Tsenova L., Young M., Kaprelyants A., Kaplan G.,
RA Mizrahi V.;
RT "The resuscitation-promoting factors of Mycobacterium tuberculosis are
RT required for virulence and resuscitation from dormancy but are collectively
RT dispensable for growth in vitro.";
RL Mol. Microbiol. 67:672-684(2008).
RN [8]
RP FUNCTION IN CELL DIVISION.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=18463693; DOI=10.1371/journal.ppat.1000001;
RA Hett E.C., Chao M.C., Deng L.L., Rubin E.J.;
RT "A mycobacterial enzyme essential for cell division synergizes with
RT resuscitation-promoting factor.";
RL PLoS Pathog. 4:E1000001-E1000001(2008).
RN [9]
RP FUNCTION AS A MURALYTIC ENZYME, AND ACTIVITY REGULATION.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=20016836; DOI=10.1371/journal.pone.0008174;
RA Demina G.R., Makarov V.A., Nikitushkin V.D., Ryabova O.B.,
RA Vostroknutova G.N., Salina E.G., Shleeva M.O., Goncharenko A.V.,
RA Kaprelyants A.S.;
RT "Finding of the low molecular weight inhibitors of resuscitation promoting
RT factor enzymatic and resuscitation activity.";
RL PLoS ONE 4:E8174-E8174(2009).
RN [10]
RP IDENTIFICATION AS A DRUG TARGET [LARGE SCALE ANALYSIS].
RX PubMed=19099550; DOI=10.1186/1752-0509-2-109;
RA Raman K., Yeturu K., Chandra N.;
RT "targetTB: a target identification pipeline for Mycobacterium tuberculosis
RT through an interactome, reactome and genome-scale structural analysis.";
RL BMC Syst. Biol. 2:109-109(2008).
RN [11]
RP ACTIVITY REGULATION.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=20686708; DOI=10.1371/journal.ppat.1001020;
RA Hett E.C., Chao M.C., Rubin E.J.;
RT "Interaction and modulation of two antagonistic cell wall enzymes of
RT mycobacteria.";
RL PLoS Pathog. 6:E1001020-E1001020(2010).
RN [12]
RP BIOTECHNOLOGY.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=21920450; DOI=10.1016/j.micinf.2011.08.011;
RA Romano M., Aryan E., Korf H., Bruffaerts N., Franken C.L., Ottenhoff T.H.,
RA Huygen K.;
RT "Potential of Mycobacterium tuberculosis resuscitation-promoting factors as
RT antigens in novel tuberculosis sub-unit vaccines.";
RL Microbes Infect. 14:86-95(2012).
RN [13]
RP STRUCTURE BY NMR OF 255-362, DISULFIDE BOND, AND BINDING TO TRI-NAG.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=15723078; DOI=10.1038/nsmb905;
RA Cohen-Gonsaud M., Barthe P., Bagneris C., Henderson B., Ward J.,
RA Roumestand C., Keep N.H.;
RT "The structure of a resuscitation-promoting factor domain from
RT Mycobacterium tuberculosis shows homology to lysozymes.";
RL Nat. Struct. Mol. Biol. 12:270-273(2005).
RN [14]
RP X-RAY CRYSTALLOGRAPHY (1.83 ANGSTROMS) OF 194-362, SUBUNIT, AND DISULFIDE
RP BOND.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=18992255; DOI=10.1016/j.jmb.2008.10.042;
RA Ruggiero A., Tizzano B., Pedone E., Pedone C., Wilmanns M., Berisio R.;
RT "Crystal structure of the resuscitation-promoting factor (DeltaDUF)RpfB
RT from M. tuberculosis.";
RL J. Mol. Biol. 385:153-162(2009).
CC -!- FUNCTION: Factor that stimulates resuscitation of dormant cells. Has
CC peptidoglycan (PG) hydrolytic activity. Active in the pM concentration
CC range. Has little to no effect on actively-growing cells. PG fragments
CC could either directly activate the resuscitation pathway of dormant
CC bacteria or serve as a substrate for endogenous Rpf, resulting in low
CC molecular weight products with resuscitation activity.
CC -!- FUNCTION: Reduces lag phase and enhances the growth of quiescent (1
CC month-old culture) M.tuberculosis; works best between 8 and 128 pM.
CC Increases the number of bacteria that can be recovered from a 3 month-
CC old culture. Stimulates growth of stationary phase M.bovis (a slowly-
CC growing Mycobacterium) as well as M.smegmatis cells (a fast grower).
CC Binds N,N',N''-triacetylchitotriose (tri-NAG). A fragment (residues
CC 194-362) hydrolyzes an artificial lysozyme substrate 4-
CC methylumbelliferyl-beta-D-N,N',N''-triacetylchitotrioside (MUF tri-
CC NAG). By itself has little activity on cell wall, in combination with
CC RipA is active against cell wall extracts from a number of
CC Actinobacteria; this activity is inhibited by PBP1A (ponA1). Sequential
CC gene disruption indicates RpfB and RpfE are higher than RpfD and RpfC
CC in functional hierarchy.
CC -!- ACTIVITY REGULATION: Activity on the artificial substrate MUF tri-NAG
CC is inhibited by 2-nitrophenylthiocyanates (NPT) compounds. The
CC synergistic effects on peptidoglycan degradation of RipA plus RpfB are
CC inhibited by addition of PBP1A (ponA1). {ECO:0000269|PubMed:20016836,
CC ECO:0000269|PubMed:20686708}.
CC -!- SUBUNIT: Monomer (Probable). Interacts with RipA.
CC {ECO:0000269|PubMed:17919286, ECO:0000269|PubMed:18992255,
CC ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000255|PROSITE-
CC ProRule:PRU00303}; Lipid-anchor {ECO:0000255|PROSITE-ProRule:PRU00303}.
CC Note=Localizes to the septa upon expression in M.smegmatis.
CC {ECO:0000269|PubMed:17919286}.
CC -!- INDUCTION: Expressed in actively growing cells.
CC {ECO:0000269|PubMed:12410821}.
CC -!- DOMAIN: An expressed fragment (residues 194-362) hydrolyzes an
CC artificial lysozyme substrate 4-methylumbelliferyl-beta-D-N,N',N''-
CC triacetylchitotrioside (MUF tri-NAG).
CC -!- DISRUPTION PHENOTYPE: Not essential, disruption of rpfB alone has no
CC effect on growth or survival in liquid culture, nor in mouse infection
CC models, colonies plated over a 52-week culture period are visibly drier
CC and more friable. Alterations in gene expression are seen. All 5 genes
CC in this family can be deleted without affecting growth in culture,
CC however triple deletion mutants (rpfA-rpfC-rpfB or rpfA-rpfC-rpfD) are
CC not able to resuscitate spontaneously in the presence or absence of
CC O(2), and are attenuated in a mouse infection model.
CC {ECO:0000269|PubMed:15207486, ECO:0000269|PubMed:18186793}.
CC -!- BIOTECHNOLOGY: A promising vaccine candidate, an rpfB-encoding DNA
CC vaccine induces elevated cellular immune responses, confers modest but
CC significant protection against intra-tracheal tuberculosis challenge in
CC female C57BL/6 and BALB/c mice. {ECO:0000269|PubMed:12874362,
CC ECO:0000269|PubMed:21920450}.
CC -!- MISCELLANEOUS: Was identified as a high-confidence drug target.
CC -!- SIMILARITY: Belongs to the transglycosylase family. Rpf subfamily.
CC {ECO:0000305}.
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DR EMBL; AL123456; CCP43759.1; -; Genomic_DNA.
DR PIR; D70603; D70603.
DR RefSeq; NP_215525.1; NC_000962.3.
DR RefSeq; WP_003405187.1; NZ_KK339370.1.
DR PDB; 1XSF; NMR; -; A=255-362.
DR PDB; 3EO5; X-ray; 1.83 A; A=194-362.
DR PDB; 4EMN; X-ray; 1.17 A; A/B/C/D=282-362.
DR PDB; 4KL7; X-ray; 1.45 A; A/B/C/D=283-362.
DR PDB; 4KPM; X-ray; 1.33 A; A/B/C/D=283-362.
DR PDB; 5E27; X-ray; 2.60 A; A/B=115-362.
DR PDBsum; 1XSF; -.
DR PDBsum; 3EO5; -.
DR PDBsum; 4EMN; -.
DR PDBsum; 4KL7; -.
DR PDBsum; 4KPM; -.
DR PDBsum; 5E27; -.
DR AlphaFoldDB; P9WG29; -.
DR SMR; P9WG29; -.
DR STRING; 83332.Rv1009; -.
DR PaxDb; P9WG29; -.
DR DNASU; 886048; -.
DR GeneID; 886048; -.
DR KEGG; mtu:Rv1009; -.
DR PATRIC; fig|83332.111.peg.1120; -.
DR TubercuList; Rv1009; -.
DR eggNOG; COG3583; Bacteria.
DR OMA; ASPWPHC; -.
DR PhylomeDB; P9WG29; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005576; C:extracellular region; IDA:MTBBASE.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016787; F:hydrolase activity; IEA:UniProtKB-KW.
DR GO; GO:0085016; P:dormancy exit of symbiont in host; IMP:MTBBASE.
DR GO; GO:0010629; P:negative regulation of gene expression; IDA:MTBBASE.
DR GO; GO:0010628; P:positive regulation of gene expression; IDA:MTBBASE.
DR GO; GO:0040010; P:positive regulation of growth rate; IDA:MTBBASE.
DR CDD; cd13925; RPF; 1.
DR InterPro; IPR007137; DUF348.
DR InterPro; IPR011098; G5_dom.
DR InterPro; IPR023346; Lysozyme-like_dom_sf.
DR InterPro; IPR010618; RPF.
DR Pfam; PF03990; DUF348; 3.
DR Pfam; PF07501; G5; 1.
DR Pfam; PF06737; Transglycosylas; 1.
DR SMART; SM01208; G5; 1.
DR SUPFAM; SSF53955; SSF53955; 1.
DR PROSITE; PS51109; G5; 1.
DR PROSITE; PS51257; PROKAR_LIPOPROTEIN; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cell membrane; Disulfide bond; Hydrolase; Lipoprotein;
KW Membrane; Palmitate; Reference proteome; Signal; Virulence.
FT SIGNAL 1..23
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00303"
FT CHAIN 24..362
FT /note="Resuscitation-promoting factor RpfB"
FT /id="PRO_0000421026"
FT DOMAIN 192..272
FT /note="G5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00437"
FT LIPID 24
FT /note="N-palmitoyl cysteine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00303"
FT LIPID 24
FT /note="S-diacylglycerol cysteine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00303"
FT DISULFID 291..355
FT /evidence="ECO:0000269|PubMed:15723078,
FT ECO:0000269|PubMed:18992255"
FT STRAND 141..145
FT /evidence="ECO:0007829|PDB:5E27"
FT HELIX 159..165
FT /evidence="ECO:0007829|PDB:5E27"
FT STRAND 175..178
FT /evidence="ECO:0007829|PDB:5E27"
FT STRAND 188..193
FT /evidence="ECO:0007829|PDB:5E27"
FT STRAND 196..206
FT /evidence="ECO:0007829|PDB:3EO5"
FT STRAND 210..215
FT /evidence="ECO:0007829|PDB:3EO5"
FT STRAND 223..227
FT /evidence="ECO:0007829|PDB:3EO5"
FT STRAND 232..243
FT /evidence="ECO:0007829|PDB:3EO5"
FT STRAND 246..259
FT /evidence="ECO:0007829|PDB:3EO5"
FT STRAND 264..269
FT /evidence="ECO:0007829|PDB:3EO5"
FT HELIX 284..293
FT /evidence="ECO:0007829|PDB:4EMN"
FT STRAND 302..304
FT /evidence="ECO:0007829|PDB:4EMN"
FT TURN 307..310
FT /evidence="ECO:0007829|PDB:4EMN"
FT HELIX 313..318
FT /evidence="ECO:0007829|PDB:4EMN"
FT HELIX 321..323
FT /evidence="ECO:0007829|PDB:4EMN"
FT HELIX 328..330
FT /evidence="ECO:0007829|PDB:4EMN"
FT HELIX 333..347
FT /evidence="ECO:0007829|PDB:4EMN"
FT HELIX 349..351
FT /evidence="ECO:0007829|PDB:4EMN"
FT HELIX 355..358
FT /evidence="ECO:0007829|PDB:4EMN"
SQ SEQUENCE 362 AA; 38078 MW; 02B55D8C70373D10 CRC64;
MLRLVVGALL LVLAFAGGYA VAACKTVTLT VDGTAMRVTT MKSRVIDIVE ENGFSVDDRD
DLYPAAGVQV HDADTIVLRR SRPLQISLDG HDAKQVWTTA STVDEALAQL AMTDTAPAAA
SRASRVPLSG MALPVVSAKT VQLNDGGLVR TVHLPAPNVA GLLSAAGVPL LQSDHVVPAA
TAPIVEGMQI QVTRNRIKKV TERLPLPPNA RRVEDPEMNM SREVVEDPGV PGTQDVTFAV
AEVNGVETGR LPVANVVVTP AHEAVVRVGT KPGTEVPPVI DGSIWDAIAG CEAGGNWAIN
TGNGYYGGVQ FDQGTWEANG GLRYAPRADL ATREEQIAVA EVTRLRQGWG AWPVCAARAG
AR
