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; Evidence={ECO:0000255|HAMAP- CC Rule:MF_00938, ECO:0000269|PubMed:21300644}; CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035; Evidence={ECO:0000255|HAMAP- CC Rule:MF_00938, ECO:0000269|PubMed:21300644}; CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108; Evidence={ECO:0000255|HAMAP- CC Rule:MF_00938, 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}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 //