PARE_FRATH
ID PARE_FRATH Reviewed; 627 AA.
AC A0A0J9WZF0;
DT 17-FEB-2016, integrated into UniProtKB/Swiss-Prot.
DT 14-OCT-2015, sequence version 1.
DT 03-AUG-2022, entry version 32.
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};
DE AltName: Full=Topoisomerase IV subunit B {ECO:0000255|HAMAP-Rule:MF_00938};
GN Name=parE {ECO:0000255|HAMAP-Rule:MF_00938}; OrderedLocusNames=FTL_1726;
OS Francisella tularensis subsp. holarctica (strain LVS).
OC Bacteria; Proteobacteria; Gammaproteobacteria; Thiotrichales;
OC Francisellaceae; Francisella.
OX NCBI_TaxID=376619;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=LVS;
RA Chain P., Larimer F., Land M., Stilwagen S., Larsson P., Bearden S.,
RA Chu M., Oyston P., Forsman M., Andersson S., Lindler L., Titball R.,
RA Garcia E.;
RT "Complete genome sequence of Francisella tularensis LVS (Live Vaccine
RT Strain).";
RL Submitted (MAR-2006) to the EMBL/GenBank/DDBJ databases.
RN [2]
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 [3]
RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 1-382 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).
RN [4]
RP X-RAY CRYSTALLOGRAPHY (2.38 ANGSTROMS) OF 1-382 IN COMPLEX WITH INHIBITOR,
RP FUNCTION, AND ACTIVITY REGULATION.
RX PubMed=24386374; DOI=10.1371/journal.pone.0084409;
RA Tari L.W., Li X., Trzoss M., Bensen D.C., Chen Z., Lam T., Zhang J.,
RA Lee S.J., Hough G., Phillipson D., Akers-Rodriguez S., Cunningham M.L.,
RA Kwan B.P., Nelson K.J., Castellano A., Locke J.B., Brown-Driver V.,
RA Murphy T.M., Ong V.S., Pillar C.M., Shinabarger D.L., Nix J.,
RA Lightstone F.C., Wong S.E., Nguyen T.B., Shaw K.J., Finn J.;
RT "Tricyclic GyrB/ParE (TriBE) inhibitors: a new class of broad-spectrum
RT dual-targeting antibacterial agents.";
RL PLoS ONE 8:E84409-E84409(2013).
CC -!- FUNCTION: Topoisomerase IV is essential for chromosome segregation. It
CC relaxes supercoiled DNA (PubMed:23352267, PubMed:23294697,
CC PubMed:24386374). Performs the decatenation events required during the
CC replication of a circular DNA molecule. {ECO:0000255|HAMAP-
CC Rule:MF_00938, ECO:0000269|PubMed:23352267,
CC ECO:0000269|PubMed:24386374, ECO:0000305|PubMed:23294697}.
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-
CC Rule:MF_00938};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_00938};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_00938};
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_00938};
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 -!- ACTIVITY REGULATION: Pyrrolopyrimidines inhibit both GyrB and its
CC paralog in topoisomerase IV (parE) (PubMed:23294697, PubMed:23352267,
CC PubMed:24386374). {ECO:0000269|PubMed:23294697,
CC ECO:0000269|PubMed:23352267, ECO:0000269|PubMed:24386374}.
CC -!- SUBUNIT: Heterotetramer composed of ParC and ParE. {ECO:0000255|HAMAP-
CC Rule:MF_00938}.
CC -!- SIMILARITY: Belongs to the type II topoisomerase family. ParE type 1
CC subfamily. {ECO:0000255|HAMAP-Rule:MF_00938}.
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DR EMBL; AM233362; CAJ80165.1; -; Genomic_DNA.
DR RefSeq; WP_010032739.1; NZ_CP009694.1.
DR PDB; 4HXZ; X-ray; 2.70 A; A/B=1-382.
DR PDB; 4HY1; X-ray; 1.90 A; A/B=1-382.
DR PDB; 4HYM; X-ray; 1.90 A; A/B=1-382.
DR PDB; 4KQV; X-ray; 2.38 A; A/B=1-382.
DR PDBsum; 4HXZ; -.
DR PDBsum; 4HY1; -.
DR PDBsum; 4HYM; -.
DR PDBsum; 4KQV; -.
DR AlphaFoldDB; A0A0J9WZF0; -.
DR SMR; A0A0J9WZF0; -.
DR KEGG; ftl:FTL_1726; -.
DR OMA; ASEDIWE; -.
DR GO; GO:0005694; C:chromosome; IEA:InterPro.
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; IEA:UniProtKB-UniRule.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0007059; P:chromosome segregation; IEA:UniProtKB-UniRule.
DR GO; GO:0006265; P:DNA topological change; IEA:UniProtKB-UniRule.
DR Gene3D; 3.30.230.10; -; 1.
DR Gene3D; 3.30.565.10; -; 1.
DR Gene3D; 3.40.50.670; -; 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_S5_D2-typ_fold.
DR InterPro; IPR014721; Ribosomal_S5_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 Pfam; PF00204; DNA_gyraseB; 1.
DR Pfam; PF00986; DNA_gyraseB_C; 1.
DR Pfam; PF02518; HATPase_c; 1.
DR Pfam; PF01751; Toprim; 1.
DR SMART; SM00387; HATPase_c; 1.
DR SMART; SM00433; TOP2c; 1.
DR SUPFAM; SSF54211; SSF54211; 1.
DR SUPFAM; SSF55874; SSF55874; 1.
DR SUPFAM; SSF56719; SSF56719; 1.
DR TIGRFAMs; TIGR01055; parE_Gneg; 1.
DR PROSITE; PS00177; TOPOISOMERASE_II; 1.
DR PROSITE; PS50880; TOPRIM; 1.
PE 1: Evidence at protein level;
KW 3D-structure; ATP-binding; DNA-binding; Isomerase; Magnesium;
KW Metal-binding; Nucleotide-binding; Topoisomerase.
FT CHAIN 1..627
FT /note="DNA topoisomerase 4 subunit B"
FT /id="PRO_0000435623"
FT DOMAIN 412..525
FT /note="Toprim"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00938"
FT BINDING 4
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00938"
FT BINDING 41
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00938"
FT BINDING 68
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00938"
FT BINDING 109..115
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00938"
FT BINDING 333
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00938"
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 613
FT /note="Interaction with DNA"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00938"
FT STRAND 9..13
FT /evidence="ECO:0007829|PDB:4HY1"
FT HELIX 16..20
FT /evidence="ECO:0007829|PDB:4HY1"
FT HELIX 22..24
FT /evidence="ECO:0007829|PDB:4HY1"
FT HELIX 32..47
FT /evidence="ECO:0007829|PDB:4HY1"
FT STRAND 53..58
FT /evidence="ECO:0007829|PDB:4HY1"
FT STRAND 64..68
FT /evidence="ECO:0007829|PDB:4HY1"
FT STRAND 76..78
FT /evidence="ECO:0007829|PDB:4HYM"
FT TURN 79..82
FT /evidence="ECO:0007829|PDB:4HY1"
FT HELIX 85..91
FT /evidence="ECO:0007829|PDB:4HY1"
FT STRAND 92..99
FT /evidence="ECO:0007829|PDB:4HY1"
FT STRAND 110..113
FT /evidence="ECO:0007829|PDB:4HY1"
FT HELIX 116..120
FT /evidence="ECO:0007829|PDB:4HY1"
FT STRAND 122..131
FT /evidence="ECO:0007829|PDB:4HY1"
FT STRAND 134..141
FT /evidence="ECO:0007829|PDB:4HY1"
FT STRAND 144..154
FT /evidence="ECO:0007829|PDB:4HY1"
FT STRAND 161..168
FT /evidence="ECO:0007829|PDB:4HY1"
FT HELIX 170..172
FT /evidence="ECO:0007829|PDB:4HY1"
FT HELIX 180..192
FT /evidence="ECO:0007829|PDB:4HY1"
FT STRAND 198..203
FT /evidence="ECO:0007829|PDB:4HY1"
FT TURN 204..207
FT /evidence="ECO:0007829|PDB:4HY1"
FT STRAND 208..212
FT /evidence="ECO:0007829|PDB:4HY1"
FT TURN 215..220
FT /evidence="ECO:0007829|PDB:4HY1"
FT HELIX 221..226
FT /evidence="ECO:0007829|PDB:4HY1"
FT STRAND 231..245
FT /evidence="ECO:0007829|PDB:4HY1"
FT STRAND 247..254
FT /evidence="ECO:0007829|PDB:4HY1"
FT STRAND 263..267
FT /evidence="ECO:0007829|PDB:4HY1"
FT HELIX 277..297
FT /evidence="ECO:0007829|PDB:4HY1"
FT HELIX 308..312
FT /evidence="ECO:0007829|PDB:4HY1"
FT STRAND 315..322
FT /evidence="ECO:0007829|PDB:4HY1"
FT TURN 330..333
FT /evidence="ECO:0007829|PDB:4HY1"
FT HELIX 340..359
FT /evidence="ECO:0007829|PDB:4HY1"
FT HELIX 361..375
FT /evidence="ECO:0007829|PDB:4HY1"
SQ SEQUENCE 627 AA; 70355 MW; 4BA9C405648B7393 CRC64;
MQNYNAKSIE VLTGLDPVKK RPGMYTNIEN PNHLIQEIID NSVDEVLAGF ASKINITLYE
DNSIEVADDG RGMPVDIHPE HKMSGIELIM TKLHSGGKFS NKNYTHSGGL HGVGVSVVNA
LSTRLEAEIK RDGNVYHIVF EDGFKTKDLE IIDNVGKKNT GTKIRFWPNK KYFDDIKVNF
KALKNLLEAK AILCKALTIK YSNEIKKEKL TWHFETGLKG YLDHKLEAET LPAEPFIIDN
FSNGDSYLDA VFCWCEDLSE SIKNSYVNLI PTPQDGTHVT GLKNGIYDAI KAYIEKNSLS
VKNIKITAND SFAQLNYVIS VKITNPQFAG QTKEKLSNKD VTNFVATAVK DLLTIWLNQN
PDEARQIVEN ISKVAQKRIN ADKKTTRKRI MNTTIRLPGK LTDCISSDVN STELFIVEGD
SAGGSAKQAR DKNFQAVLPL KGKILNSWEL DADTIMNSQE IHNIATAIGV DPDSDDISAL
RYNKICILAD ADSDGLHIAT LLCAMFLKHF RKLIENGHIY IAQPPLFRID IGKSTFYALD
ENERDTILTK NSKLPGKVNI MRFKGLGEMN PAQLRESAMD VSSRRLLQLT ISDVYDDTEM
LDMLLAKKRA KDRRDWLENY GDRASVE
