ID PARE_ECOLI Reviewed; 630 AA.
AC P20083; Q2M9H0;
DT 01-FEB-1991, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1994, sequence version 3.
DT 24-JAN-2024, entry version 194.
DE RecName: Full=DNA topoisomerase 4 subunit B {ECO:0000255|HAMAP-Rule:MF_00938};
DE EC=5.6.2.2 {ECO:0000255|HAMAP-Rule:MF_00938, ECO:0000269|PubMed:15105144, ECO:0000269|PubMed:21300644};
DE AltName: Full=Topoisomerase IV subunit B {ECO:0000255|HAMAP-Rule:MF_00938};
GN Name=parE {ECO:0000255|HAMAP-Rule:MF_00938}; Synonyms=nfxD;
GN OrderedLocusNames=b3030, JW2998;
OS Escherichia coli (strain K12).
OC Bacteria; Pseudomonadota; Gammaproteobacteria; Enterobacterales;
OC Enterobacteriaceae; Escherichia.
OX NCBI_TaxID=83333;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-602.
RC STRAIN=K12;
RX PubMed=2170028; DOI=10.1016/0092-8674(90)90172-b;
RA Kato J., Nishimura Y., Imamura R., Niki H., Hiraga S., Suzuki H.;
RT "New topoisomerase essential for chromosome segregation in E. coli.";
RL Cell 63:393-404(1990).
RN [2]
RP SEQUENCE REVISION TO C-TERMINUS.
RX PubMed=8388096; DOI=10.1093/nar/21.8.1805;
RA Springer A.L., Schmid M.B.;
RT "Molecular characterization of the Salmonella typhimurium parE gene.";
RL Nucleic Acids Res. 21:1805-1809(1993).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=K12 / MG1655 / ATCC 47076;
RX PubMed=9278503; DOI=10.1126/science.277.5331.1453;
RA Blattner F.R., Plunkett G. III, Bloch C.A., Perna N.T., Burland V.,
RA Riley M., Collado-Vides J., Glasner J.D., Rode C.K., Mayhew G.F.,
RA Gregor J., Davis N.W., Kirkpatrick H.A., Goeden M.A., Rose D.J., Mau B.,
RA Shao Y.;
RT "The complete genome sequence of Escherichia coli K-12.";
RL Science 277:1453-1462(1997).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=K12 / W3110 / ATCC 27325 / DSM 5911;
RX PubMed=16738553; DOI=10.1038/msb4100049;
RA Hayashi K., Morooka N., Yamamoto Y., Fujita K., Isono K., Choi S.,
RA Ohtsubo E., Baba T., Wanner B.L., Mori H., Horiuchi T.;
RT "Highly accurate genome sequences of Escherichia coli K-12 strains MG1655
RT and W3110.";
RL Mol. Syst. Biol. 2:E1-E5(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 588-630, AND CHARACTERIZATION.
RC STRAIN=K12;
RX PubMed=8227000; DOI=10.1016/s0021-9258(20)80551-1;
RA Peng H., Marians K.J.;
RT "Escherichia coli topoisomerase IV. Purification, characterization, subunit
RT structure, and subunit interactions.";
RL J. Biol. Chem. 268:24481-24490(1993).
RN [6]
RP FUNCTION.
RX PubMed=9334322; DOI=10.1101/gad.11.19.2580;
RA Zechiedrich E.L., Khodursky A.B., Cozzarelli N.R.;
RT "Topoisomerase IV, not gyrase, decatenates products of site-specific
RT recombination in Escherichia coli.";
RL Genes Dev. 11:2580-2592(1997).
RN [7]
RP FUNCTION, SUBUNIT, COFACTOR, PUTATIVE METAL-BINDING SITES, AND CATALYTIC
RP ACTIVITY.
RX PubMed=21300644; DOI=10.1093/nar/gkr018;
RA Pitts S.L., Liou G.F., Mitchenall L.A., Burgin A.B., Maxwell A.,
RA Neuman K.C., Osheroff N.;
RT "Use of divalent metal ions in the DNA cleavage reaction of topoisomerase
RT IV.";
RL Nucleic Acids Res. 39:4808-4817(2011).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 1-390 IN COMPLEXES WITH NOVOBIOCIN
RP AND ATP ANALOG, CATALYTIC ACTIVITY, FUNCTION, AND SUBUNIT.
RX PubMed=15105144; DOI=10.1128/aac.48.5.1856-1864.2004;
RA Bellon S., Parsons J.D., Wei Y., Hayakawa K., Swenson L.L., Charifson P.S.,
RA Lippke J.A., Aldape R., Gross C.H.;
RT "Crystal structures of Escherichia coli topoisomerase IV ParE subunit (24
RT and 43 kilodaltons): a single residue dictates differences in novobiocin
RT potency against topoisomerase IV and DNA gyrase.";
RL Antimicrob. Agents Chemother. 48:1856-1864(2004).
RN [9]
RP VARIANT QUINOLONE-RESISTANT HIS-445.
RX PubMed=8980775; DOI=10.1128/aac.41.1.175;
RA Breines D.M., Ouabdesselam S., Ng E.Y., Tankovic J., Shah S., Soussy C.J.,
RA Hooper D.C.;
RT "Quinolone resistance locus nfxD of Escherichia coli is a mutant allele of
RT the parE gene encoding a subunit of topoisomerase IV.";
RL Antimicrob. Agents Chemother. 41:175-179(1997).
RN [10]
RP FUNCTION MODIFIED BY MUKB.
RX PubMed=20921377; DOI=10.1073/pnas.1008678107;
RA Li Y., Stewart N.K., Berger A.J., Vos S., Schoeffler A.J., Berger J.M.,
RA Chait B.T., Oakley M.G.;
RT "Escherichia coli condensin MukB stimulates topoisomerase IV activity by a
RT direct physical interaction.";
RL Proc. Natl. Acad. Sci. U.S.A. 107:18832-18837(2010).
RN [11]
RP FUNCTION, AND ACTIVITY REGULATION.
RX PubMed=23294697; DOI=10.1016/j.bmcl.2012.11.073;
RA Trzoss M., Bensen D.C., Li X., Chen Z., Lam T., Zhang J., Creighton C.J.,
RA Cunningham M.L., Kwan B., Stidham M., Nelson K., Brown-Driver V.,
RA Castellano A., Shaw K.J., Lightstone F.C., Wong S.E., Nguyen T.B., Finn J.,
RA Tari L.W.;
RT "Pyrrolopyrimidine inhibitors of DNA gyrase B (GyrB) and topoisomerase IV
RT (ParE), Part II: development of inhibitors with broad spectrum, Gram-
RT negative antibacterial activity.";
RL Bioorg. Med. Chem. Lett. 23:1537-1543(2013).
RN [12]
RP X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) OF 12-216 IN COMPLEX WITH INHIBITOR,
RP FUNCTION, AND ACTIVITY REGULATION.
RX PubMed=23352267; DOI=10.1016/j.bmcl.2012.11.032;
RA Tari L.W., Trzoss M., Bensen D.C., Li X., Chen Z., Lam T., Zhang J.,
RA Creighton C.J., Cunningham M.L., Kwan B., Stidham M., Shaw K.J.,
RA Lightstone F.C., Wong S.E., Nguyen T.B., Nix J., Finn J.;
RT "Pyrrolopyrimidine inhibitors of DNA gyrase B (GyrB) and topoisomerase IV
RT (ParE). Part I: Structure guided discovery and optimization of dual
RT targeting agents with potent, broad-spectrum enzymatic activity.";
RL Bioorg. Med. Chem. Lett. 23:1529-1536(2013).
CC -!- FUNCTION: Topoisomerase IV is essential for chromosome segregation; it
CC is the principal protein responsible for decatenating newly replicated
CC chromosomes (PubMed:9334322). It relaxes supercoiled DNA
CC (PubMed:15105144, PubMed:21300644, PubMed:23294697, PubMed:23352267).
CC MukB stimulates the relaxation activity of topoisomerase IV and also
CC has a modest effect on decatenation (PubMed:20921377).
CC {ECO:0000269|PubMed:15105144, ECO:0000269|PubMed:20921377,
CC ECO:0000269|PubMed:21300644, ECO:0000269|PubMed:23294697,
CC ECO:0000269|PubMed:23352267, ECO:0000269|PubMed:9334322}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP-dependent breakage, passage and rejoining of double-
CC stranded DNA.; EC=5.6.2.2; Evidence={ECO:0000255|HAMAP-Rule:MF_00938,
CC ECO:0000269|PubMed:15105144, ECO:0000269|PubMed:21300644};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_00938,
CC ECO:0000269|PubMed:21300644};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_00938,
CC ECO:0000269|PubMed:21300644};
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_00938,
CC ECO:0000269|PubMed:21300644};
CC Note=Binds two Mg(2+) per subunit. The magnesium ions form salt bridges
CC with both the protein and the DNA. Can also accept other divalent metal
CC cations, such as Mn(2+) or Ca(2+). {ECO:0000255|HAMAP-Rule:MF_00938,
CC ECO:0000269|PubMed:21300644};
CC -!- ACTIVITY REGULATION: Pyrrolopyrimidines inhibit both GyrB and its
CC paralog in topoisomerase IV (parE) (PubMed:23294697).
CC {ECO:0000269|PubMed:23294697}.
CC -!- SUBUNIT: Heterotetramer composed of ParC and ParE. {ECO:0000255|HAMAP-
CC Rule:MF_00938, ECO:0000269|PubMed:15105144,
CC ECO:0000269|PubMed:21300644}.
CC -!- INTERACTION:
CC P20083; P76015: dhaK; NbExp=3; IntAct=EBI-547277, EBI-544485;
CC -!- SIMILARITY: Belongs to the type II topoisomerase family. ParE type 1
CC subfamily. {ECO:0000255|HAMAP-Rule:MF_00938}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA24298.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; M58409; AAA24298.1; ALT_FRAME; Genomic_DNA.
DR EMBL; U28377; AAA69198.1; -; Genomic_DNA.
DR EMBL; U00096; AAC76066.1; -; Genomic_DNA.
DR EMBL; AP009048; BAE77086.1; -; Genomic_DNA.
DR EMBL; L22026; AAC36841.1; -; Unassigned_DNA.
DR PIR; D65090; D65090.
DR RefSeq; NP_417502.1; NC_000913.3.
DR RefSeq; WP_000195296.1; NZ_SSUR01000002.1.
DR PDB; 1S14; X-ray; 2.00 A; A/B=1-217.
DR PDB; 1S16; X-ray; 2.10 A; A/B=1-390.
DR PDB; 3FV5; X-ray; 1.80 A; A/B=15-215.
DR PDB; 4HZ0; X-ray; 2.20 A; A/B=12-216.
DR PDBsum; 1S14; -.
DR PDBsum; 1S16; -.
DR PDBsum; 3FV5; -.
DR PDBsum; 4HZ0; -.
DR AlphaFoldDB; P20083; -.
DR SMR; P20083; -.
DR BioGRID; 4262393; 305.
DR BioGRID; 851818; 2.
DR ComplexPortal; CPX-1104; Topoisomerase IV.
DR DIP; DIP-10441N; -.
DR IntAct; P20083; 25.
DR STRING; 511145.b3030; -.
DR BindingDB; P20083; -.
DR ChEMBL; CHEMBL3329081; -.
DR DrugBank; DB04395; Phosphoaminophosphonic Acid-Adenylate Ester.
DR DrugCentral; P20083; -.
DR jPOST; P20083; -.
DR PaxDb; 511145-b3030; -.
DR EnsemblBacteria; AAC76066; AAC76066; b3030.
DR GeneID; 75203576; -.
DR GeneID; 947501; -.
DR KEGG; ecj:JW2998; -.
DR KEGG; eco:b3030; -.
DR PATRIC; fig|1411691.4.peg.3701; -.
DR EchoBASE; EB0681; -.
DR eggNOG; COG0187; Bacteria.
DR HOGENOM; CLU_006146_4_1_6; -.
DR InParanoid; P20083; -.
DR OMA; NTWEVDG; -.
DR OrthoDB; 9802808at2; -.
DR PhylomeDB; P20083; -.
DR BioCyc; EcoCyc:EG10687-MONOMER; -.
DR EvolutionaryTrace; P20083; -.
DR PRO; PR:P20083; -.
DR Proteomes; UP000000318; Chromosome.
DR Proteomes; UP000000625; Chromosome.
DR GO; GO:0005694; C:chromosome; IEA:InterPro.
DR GO; GO:0005829; C:cytosol; IDA:EcoCyc.
DR GO; GO:0009330; C:DNA topoisomerase type II (double strand cut, ATP-hydrolyzing) complex; NAS:ComplexPortal.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-UniRule.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-UniRule.
DR GO; GO:0003918; F:DNA topoisomerase type II (double strand cut, ATP-hydrolyzing) activity; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0051276; P:chromosome organization; IMP:EcoliWiki.
DR GO; GO:0007059; P:chromosome segregation; IEA:UniProtKB-UniRule.
DR GO; GO:0006265; P:DNA topological change; IBA:GO_Central.
DR GO; GO:0030541; P:plasmid partitioning; IDA:EcoliWiki.
DR GO; GO:0046677; P:response to antibiotic; IEA:UniProtKB-KW.
DR GO; GO:0007062; P:sister chromatid cohesion; IMP:EcoliWiki.
DR CDD; cd16928; HATPase_GyrB-like; 1.
DR CDD; cd00822; TopoII_Trans_DNA_gyrase; 1.
DR Gene3D; 3.30.230.10; -; 1.
DR Gene3D; 3.40.50.670; -; 1.
DR Gene3D; 3.30.565.10; Histidine kinase-like ATPase, C-terminal domain; 1.
DR HAMAP; MF_00938; ParE_type1; 1.
DR InterPro; IPR002288; DNA_gyrase_B_C.
DR InterPro; IPR003594; HATPase_C.
DR InterPro; IPR036890; HATPase_C_sf.
DR InterPro; IPR020568; Ribosomal_Su5_D2-typ_SF.
DR InterPro; IPR014721; Ribsml_uS5_D2-typ_fold_subgr.
DR InterPro; IPR001241; Topo_IIA.
DR InterPro; IPR013760; Topo_IIA-like_dom_sf.
DR InterPro; IPR013759; Topo_IIA_B_C.
DR InterPro; IPR013506; Topo_IIA_bsu_dom2.
DR InterPro; IPR018522; TopoIIA_CS.
DR InterPro; IPR005737; TopoIV_B_Gneg.
DR InterPro; IPR006171; TOPRIM_domain.
DR NCBIfam; TIGR01055; parE_Gneg; 1.
DR PANTHER; PTHR45866; DNA GYRASE/TOPOISOMERASE SUBUNIT B; 1.
DR PANTHER; PTHR45866:SF4; DNA TOPOISOMERASE 4 SUBUNIT B; 1.
DR Pfam; PF00204; DNA_gyraseB; 1.
DR Pfam; PF00986; DNA_gyraseB_C; 1.
DR Pfam; PF02518; HATPase_c; 1.
DR Pfam; PF01751; Toprim; 1.
DR PRINTS; PR01098; TOPISMRASE4B.
DR PRINTS; PR00418; TPI2FAMILY.
DR SMART; SM00387; HATPase_c; 1.
DR SMART; SM00433; TOP2c; 1.
DR SUPFAM; SSF55874; ATPase domain of HSP90 chaperone/DNA topoisomerase II/histidine kinase; 1.
DR SUPFAM; SSF54211; Ribosomal protein S5 domain 2-like; 1.
DR SUPFAM; SSF56719; Type II DNA topoisomerase; 1.
DR PROSITE; PS00177; TOPOISOMERASE_II; 1.
DR PROSITE; PS50880; TOPRIM; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Antibiotic resistance; ATP-binding; DNA-binding; Isomerase;
KW Magnesium; Metal-binding; Nucleotide-binding; Reference proteome;
KW Topoisomerase.
FT CHAIN 1..630
FT /note="DNA topoisomerase 4 subunit B"
FT /id="PRO_0000145427"
FT DOMAIN 412..525
FT /note="Toprim"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00938"
FT BINDING 5
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000305|PubMed:15105144"
FT BINDING 42
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000305|PubMed:15105144"
FT BINDING 69
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000305|PubMed:15105144"
FT BINDING 110..116
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000305|PubMed:15105144"
FT BINDING 334
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000305|PubMed:15105144"
FT BINDING 418
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00938"
FT BINDING 490
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00938"
FT BINDING 490
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00938"
FT BINDING 492
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00938"
FT SITE 443
FT /note="Interaction with DNA"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00938"
FT SITE 446
FT /note="Interaction with DNA"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00938"
FT SITE 497
FT /note="Interaction with DNA"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00938"
FT SITE 615
FT /note="Interaction with DNA"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00938"
FT VARIANT 445
FT /note="L -> H (in strain: DH161; quinolone-resistant)"
FT /evidence="ECO:0000269|PubMed:8980775"
FT HELIX 7..9
FT /evidence="ECO:0007829|PDB:1S16"
FT HELIX 17..21
FT /evidence="ECO:0007829|PDB:3FV5"
FT HELIX 23..25
FT /evidence="ECO:0007829|PDB:3FV5"
FT HELIX 33..48
FT /evidence="ECO:0007829|PDB:3FV5"
FT STRAND 53..59
FT /evidence="ECO:0007829|PDB:3FV5"
FT STRAND 65..69
FT /evidence="ECO:0007829|PDB:3FV5"
FT TURN 80..82
FT /evidence="ECO:0007829|PDB:1S14"
FT STRAND 83..85
FT /evidence="ECO:0007829|PDB:3FV5"
FT HELIX 86..92
FT /evidence="ECO:0007829|PDB:3FV5"
FT STRAND 96..98
FT /evidence="ECO:0007829|PDB:1S16"
FT STRAND 100..104
FT /evidence="ECO:0007829|PDB:1S16"
FT STRAND 106..108
FT /evidence="ECO:0007829|PDB:4HZ0"
FT HELIX 117..121
FT /evidence="ECO:0007829|PDB:3FV5"
FT STRAND 123..132
FT /evidence="ECO:0007829|PDB:3FV5"
FT STRAND 135..142
FT /evidence="ECO:0007829|PDB:3FV5"
FT STRAND 145..155
FT /evidence="ECO:0007829|PDB:3FV5"
FT STRAND 162..169
FT /evidence="ECO:0007829|PDB:3FV5"
FT HELIX 171..173
FT /evidence="ECO:0007829|PDB:3FV5"
FT HELIX 181..194
FT /evidence="ECO:0007829|PDB:3FV5"
FT STRAND 199..204
FT /evidence="ECO:0007829|PDB:3FV5"
FT TURN 205..208
FT /evidence="ECO:0007829|PDB:3FV5"
FT STRAND 209..213
FT /evidence="ECO:0007829|PDB:3FV5"
FT HELIX 219..227
FT /evidence="ECO:0007829|PDB:1S16"
FT STRAND 233..243
FT /evidence="ECO:0007829|PDB:1S16"
FT STRAND 245..255
FT /evidence="ECO:0007829|PDB:1S16"
FT STRAND 264..268
FT /evidence="ECO:0007829|PDB:1S16"
FT HELIX 278..297
FT /evidence="ECO:0007829|PDB:1S16"
FT HELIX 309..313
FT /evidence="ECO:0007829|PDB:1S16"
FT STRAND 316..326
FT /evidence="ECO:0007829|PDB:1S16"
FT STRAND 329..331
FT /evidence="ECO:0007829|PDB:1S16"
FT HELIX 342..359
FT /evidence="ECO:0007829|PDB:1S16"
FT HELIX 362..382
FT /evidence="ECO:0007829|PDB:1S16"
SQ SEQUENCE 630 AA; 70244 MW; 3F83D108BC1C6A41 CRC64;
MTQTYNADAI EVLTGLEPVR RRPGMYTDTT RPNHLGQEVI DNSVDEALAG HAKRVDVILH
ADQSLEVIDD GRGMPVDIHP EEGVPAVELI LCRLHAGGKF SNKNYQFSGG LHGVGISVVN
ALSKRVEVNV RRDGQVYNIA FENGEKVQDL QVVGTCGKRN TGTSVHFWPD ETFFDSPRFS
VSRLTHVLKA KAVLCPGVEI TFKDEINNTE QRWCYQDGLN DYLAEAVNGL PTLPEKPFIG
NFAGDTEAVD WALLWLPEGG ELLTESYVNL IPTMQGGTHV NGLRQGLLDA MREFCEYRNI
LPRGVKLSAE DIWDRCAYVL SVKMQDPQFA GQTKERLSSR QCAAFVSGVV KDAFILWLNQ
NVQAAELLAE MAISSAQRRM RAAKKVVRKK LTSGPALPGK LADCTAQDLN RTELFLVEGD
SAGGSAKQAR DREYQAIMPL KGKILNTWEV SSDEVLASQE VHDISVAIGI DPDSDDLSQL
RYGKICILAD ADSDGLHIAT LLCALFVKHF RALVKHGHVY VALPPLYRID LGKEVYYALT
EEEKEGVLEQ LKRKKGKPNV QRFKGLGEMN PMQLRETTLD PNTRRLVQLT IDDEDDQRTD
AMMDMLLAKK RSEDRRNWLQ EKGDMAEIEV
//
