ID   PARC_STRPN              Reviewed;         823 AA.
AC   P72525; P72537; Q54917;
DT   15-DEC-1998, integrated into UniProtKB/Swiss-Prot.
DT   26-SEP-2001, sequence version 3.
DT   27-MAR-2024, entry version 165.
DE   RecName: Full=DNA topoisomerase 4 subunit A {ECO:0000255|HAMAP-Rule:MF_00937};
DE            EC=5.6.2.2 {ECO:0000255|HAMAP-Rule:MF_00937};
DE   AltName: Full=Topoisomerase IV subunit A {ECO:0000255|HAMAP-Rule:MF_00937};
GN   Name=parC {ECO:0000255|HAMAP-Rule:MF_00937};
GN   OrderedLocusNames=SP_0855;
OS   Streptococcus pneumoniae serotype 4 (strain ATCC BAA-334 / TIGR4).
OC   Bacteria; Bacillota; Bacilli; Lactobacillales; Streptococcaceae;
OC   Streptococcus.
OX   NCBI_TaxID=170187;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   STRAIN=7785;
RX   PubMed=8763932; DOI=10.1128/jb.178.14.4060-4069.1996;
RA   Pan X., Fisher M.;
RT   "Cloning and characterization of the parC and parE genes of Streptococcus
RT   pneumoniae encoding DNA topoisomerase IV: role in fluoroquinolone
RT   resistance.";
RL   J. Bacteriol. 178:4060-4069(1996).
RN   [2]
RP   SEQUENCE REVISION TO 636-643.
RA   Pan X.;
RL   Submitted (JAN-2000) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC BAA-334 / TIGR4;
RX   PubMed=11463916; DOI=10.1126/science.1061217;
RA   Tettelin H., Nelson K.E., Paulsen I.T., Eisen J.A., Read T.D.,
RA   Peterson S.N., Heidelberg J.F., DeBoy R.T., Haft D.H., Dodson R.J.,
RA   Durkin A.S., Gwinn M.L., Kolonay J.F., Nelson W.C., Peterson J.D.,
RA   Umayam L.A., White O., Salzberg S.L., Lewis M.R., Radune D.,
RA   Holtzapple E.K., Khouri H.M., Wolf A.M., Utterback T.R., Hansen C.L.,
RA   McDonald L.A., Feldblyum T.V., Angiuoli S.V., Dickinson T., Hickey E.K.,
RA   Holt I.E., Loftus B.J., Yang F., Smith H.O., Venter J.C., Dougherty B.A.,
RA   Morrison D.A., Hollingshead S.K., Fraser C.M.;
RT   "Complete genome sequence of a virulent isolate of Streptococcus
RT   pneumoniae.";
RL   Science 293:498-506(2001).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-620.
RC   STRAIN=D39 / NCTC 7466 / Serotype 2;
RX   PubMed=8891124; DOI=10.1128/aac.40.10.2252;
RA   Munoz R., de la Campa A.G.;
RT   "ParC subunit of DNA topoisomerase IV of Streptococcus pneumoniae is a
RT   primary target of fluoroquinolones and cooperates with DNA gyrase A subunit
RT   in forming resistance phenotype.";
RL   Antimicrob. Agents Chemother. 40:2252-2257(1996).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 38-106.
RC   STRAIN=BM4203;
RX   PubMed=8913454; DOI=10.1128/aac.40.11.2505;
RA   Tankovic J., Perichon B., Duval J., Courvalin P.;
RT   "Contribution of mutations in gyrA and parC genes to fluoroquinolone
RT   resistance of mutants of Streptococcus pneumoniae obtained in vivo and in
RT   vitro.";
RL   Antimicrob. Agents Chemother. 40:2505-2510(1996).
RN   [6]
RP   X-RAY CRYSTALLOGRAPHY (2.67 ANGSTROMS) OF 1-488, FUNCTION, CATALYTIC
RP   ACTIVITY, AND SUBUNIT.
RX   PubMed=17375187; DOI=10.1371/journal.pone.0000301;
RA   Laponogov I., Veselkov D.A., Sohi M.K., Pan X.S., Achari A., Yang C.,
RA   Ferrara J.D., Fisher L.M., Sanderson M.R.;
RT   "Breakage-reunion domain of Streptococcus pneumoniae topoisomerase IV:
RT   crystal structure of a gram-positive quinolone target.";
RL   PLoS ONE 2:E301-E301(2007).
RN   [7]
RP   X-RAY CRYSTALLOGRAPHY (4.0 ANGSTROMS) OF 1-488.
RX   PubMed=19448616; DOI=10.1038/nsmb.1604;
RA   Laponogov I., Sohi M.K., Veselkov D.A., Pan X.S., Sawhney R.,
RA   Thompson A.W., McAuley K.E., Fisher L.M., Sanderson M.R.;
RT   "Structural insight into the quinolone-DNA cleavage complex of type IIA
RT   topoisomerases.";
RL   Nat. Struct. Mol. Biol. 16:667-669(2009).
RN   [8]
RP   X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 1-488 IN COMPLEX WITH PARE;
RP   LEVOFLOXACIN AND DNA, CATALYTIC ACTIVITY, FUNCTION, ACTIVE SITE, ACTIVITY
RP   REGULATION, AND SUBUNIT.
RX   PubMed=20596531; DOI=10.1371/journal.pone.0011338;
RA   Laponogov I., Pan X.S., Veselkov D.A., McAuley K.E., Fisher L.M.,
RA   Sanderson M.R.;
RT   "Structural basis of gate-DNA breakage and resealing by type II
RT   topoisomerases.";
RL   PLoS ONE 5:E11338-E11338(2010).
CC   -!- FUNCTION: Topoisomerase IV is essential for chromosome segregation. It
CC       relaxes supercoiled DNA (PubMed:17375187, PubMed:20596531). Performs
CC       the decatenation events required during the replication of a circular
CC       DNA molecule. {ECO:0000255|HAMAP-Rule:MF_00937,
CC       ECO:0000269|PubMed:17375187, ECO:0000269|PubMed:20596531}.
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_00937,
CC         ECO:0000269|PubMed:17375187, ECO:0000269|PubMed:20596531};
CC   -!- ACTIVITY REGULATION: Inhibited by quinolones, such as levofloxacin
CC       (PubMed:20596531). {ECO:0000269|PubMed:20596531}.
CC   -!- SUBUNIT: Heterotetramer composed of ParC and ParE (PubMed:17375187,
CC       PubMed:20596531). {ECO:0000255|HAMAP-Rule:MF_00937,
CC       ECO:0000269|PubMed:17375187, ECO:0000269|PubMed:20596531}.
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000255|HAMAP-Rule:MF_00937};
CC       Peripheral membrane protein {ECO:0000255|HAMAP-Rule:MF_00937}.
CC   -!- SIMILARITY: Belongs to the type II topoisomerase GyrA/ParC subunit
CC       family. ParC type 2 subfamily. {ECO:0000255|HAMAP-Rule:MF_00937}.
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DR   EMBL; Z67739; CAA91551.2; -; Genomic_DNA.
DR   EMBL; AE005672; AAK74984.1; -; Genomic_DNA.
DR   EMBL; X95717; CAA65021.1; -; Genomic_DNA.
DR   EMBL; U49088; AAB08038.1; -; Genomic_DNA.
DR   PIR; G95098; G95098.
DR   PDB; 2NOV; X-ray; 2.67 A; A/B/C/D=1-488.
DR   PDB; 3FOE; X-ray; 4.00 A; A/B=1-488.
DR   PDB; 3FOF; X-ray; 4.00 A; A/B=1-488.
DR   PDB; 3K9F; X-ray; 2.90 A; A/B=1-488.
DR   PDB; 3KSA; X-ray; 3.30 A; A/B=1-488.
DR   PDB; 3KSB; X-ray; 3.50 A; A/B=1-488.
DR   PDB; 3LTN; X-ray; 3.10 A; A/B=1-488.
DR   PDB; 3RAD; X-ray; 3.35 A; A/B=1-488.
DR   PDB; 3RAE; X-ray; 2.90 A; A/B=1-488.
DR   PDB; 3RAF; X-ray; 3.24 A; A/B=1-488.
DR   PDB; 4I3H; X-ray; 3.70 A; A/B=1-490.
DR   PDB; 4JUO; X-ray; 6.53 A; A=1-488.
DR   PDB; 4KOE; X-ray; 3.02 A; A/B=1-488.
DR   PDB; 4KPE; X-ray; 3.43 A; A/B=1-488.
DR   PDB; 4KPF; X-ray; 3.24 A; A/B=1-488.
DR   PDB; 4Z3O; X-ray; 3.44 A; A/B=3-484.
DR   PDB; 4Z4Q; X-ray; 3.04 A; A/B=3-484.
DR   PDB; 4Z53; X-ray; 3.26 A; A/B=3-484.
DR   PDBsum; 2NOV; -.
DR   PDBsum; 3FOE; -.
DR   PDBsum; 3FOF; -.
DR   PDBsum; 3K9F; -.
DR   PDBsum; 3KSA; -.
DR   PDBsum; 3KSB; -.
DR   PDBsum; 3LTN; -.
DR   PDBsum; 3RAD; -.
DR   PDBsum; 3RAE; -.
DR   PDBsum; 3RAF; -.
DR   PDBsum; 4I3H; -.
DR   PDBsum; 4JUO; -.
DR   PDBsum; 4KOE; -.
DR   PDBsum; 4KPE; -.
DR   PDBsum; 4KPF; -.
DR   PDBsum; 4Z3O; -.
DR   PDBsum; 4Z4Q; -.
DR   PDBsum; 4Z53; -.
DR   AlphaFoldDB; P72525; -.
DR   SMR; P72525; -.
DR   DIP; DIP-48521N; -.
DR   IntAct; P72525; 1.
DR   ChEMBL; CHEMBL2363033; -.
DR   DrugBank; DB06771; Besifloxacin.
DR   DrugBank; DB01044; Gatifloxacin.
DR   DrugCentral; P72525; -.
DR   PaxDb; 170187-SP_0855; -.
DR   EnsemblBacteria; AAK74984; AAK74984; SP_0855.
DR   KEGG; spn:SP_0855; -.
DR   eggNOG; COG0188; Bacteria.
DR   PhylomeDB; P72525; -.
DR   BioCyc; SPNE170187:G1FZB-873-MONOMER; -.
DR   EvolutionaryTrace; P72525; -.
DR   PRO; PR:P72525; -.
DR   Proteomes; UP000000585; Chromosome.
DR   GO; GO:0005694; C:chromosome; IEA:InterPro.
DR   GO; GO:0019897; C:extrinsic component of plasma membrane; IEA:UniProtKB-UniRule.
DR   GO; GO:0005524; F:ATP binding; IEA:InterPro.
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:0007059; P:chromosome segregation; IEA:UniProtKB-UniRule.
DR   GO; GO:0006265; P:DNA topological change; IEA:UniProtKB-UniRule.
DR   CDD; cd00187; TOP4c; 1.
DR   Gene3D; 3.30.1360.40; -; 1.
DR   Gene3D; 2.120.10.90; DNA gyrase/topoisomerase IV, subunit A, C-terminal; 1.
DR   Gene3D; 3.90.199.10; Topoisomerase II, domain 5; 1.
DR   Gene3D; 1.10.268.10; Topoisomerase, domain 3; 1.
DR   HAMAP; MF_00937; ParC_type2; 1.
DR   InterPro; IPR006691; GyrA/parC_rep.
DR   InterPro; IPR035516; Gyrase/topoIV_suA_C.
DR   InterPro; IPR013760; Topo_IIA-like_dom_sf.
DR   InterPro; IPR013758; Topo_IIA_A/C_ab.
DR   InterPro; IPR013757; Topo_IIA_A_a_sf.
DR   InterPro; IPR002205; Topo_IIA_dom_A.
DR   InterPro; IPR005741; TopoIV_A_Gpos.
DR   NCBIfam; TIGR01061; parC_Gpos; 1.
DR   PANTHER; PTHR43493; DNA GYRASE/TOPOISOMERASE SUBUNIT A; 1.
DR   PANTHER; PTHR43493:SF9; DNA TOPOISOMERASE 4 SUBUNIT A; 1.
DR   Pfam; PF03989; DNA_gyraseA_C; 5.
DR   Pfam; PF00521; DNA_topoisoIV; 1.
DR   SMART; SM00434; TOP4c; 1.
DR   SUPFAM; SSF101904; GyrA/ParC C-terminal domain-like; 1.
DR   SUPFAM; SSF56719; Type II DNA topoisomerase; 1.
DR   PROSITE; PS52040; TOPO_IIA; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Cell membrane; DNA-binding; Isomerase; Membrane;
KW   Reference proteome; Topoisomerase.
FT   CHAIN           1..823
FT                   /note="DNA topoisomerase 4 subunit A"
FT                   /id="PRO_0000145418"
FT   DOMAIN          30..496
FT                   /note="Topo IIA-type catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01384"
FT   ACT_SITE        118
FT                   /note="O-(5'-phospho-DNA)-tyrosine intermediate"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_00937,
FT                   ECO:0000269|PubMed:20596531"
FT   SITE            38
FT                   /note="Interaction with DNA"
FT   SITE            74
FT                   /note="Interaction with DNA"
FT   SITE            76
FT                   /note="Interaction with DNA"
FT   SITE            87
FT                   /note="Interaction with DNA"
FT   SITE            93
FT                   /note="Interaction with DNA"
FT   SITE            117
FT                   /note="Transition state stabilizer"
FT   CONFLICT        95
FT                   /note="R -> C (in Ref. 5; AAB08038)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        257
FT                   /note="I -> T (in Ref. 1; CAA91551 and 4; CAA65021)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        362
FT                   /note="R -> P (in Ref. 4; CAA65021)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        373
FT                   /note="H -> R (in Ref. 4; CAA65021)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        401
FT                   /note="A -> P (in Ref. 4; CAA65021)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        473
FT                   /note="K -> N (in Ref. 4; CAA65021)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        589
FT                   /note="E -> A (in Ref. 4; CAA65021)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        608
FT                   /note="V -> A (in Ref. 4; CAA65021)"
FT                   /evidence="ECO:0000305"
FT   STRAND          4..8
FT                   /evidence="ECO:0007829|PDB:3K9F"
FT   HELIX           9..26
FT                   /evidence="ECO:0007829|PDB:3K9F"
FT   TURN            27..29
FT                   /evidence="ECO:0007829|PDB:3RAF"
FT   TURN            33..35
FT                   /evidence="ECO:0007829|PDB:3K9F"
FT   HELIX           39..50
FT                   /evidence="ECO:0007829|PDB:3K9F"
FT   HELIX           62..72
FT                   /evidence="ECO:0007829|PDB:3K9F"
FT   HELIX           78..88
FT                   /evidence="ECO:0007829|PDB:3K9F"
FT   TURN            91..93
FT                   /evidence="ECO:0007829|PDB:3K9F"
FT   STRAND          98..103
FT                   /evidence="ECO:0007829|PDB:3K9F"
FT   TURN            116..118
FT                   /evidence="ECO:0007829|PDB:3K9F"
FT   STRAND          120..123
FT                   /evidence="ECO:0007829|PDB:3K9F"
FT   HELIX           125..130
FT                   /evidence="ECO:0007829|PDB:3K9F"
FT   TURN            131..133
FT                   /evidence="ECO:0007829|PDB:3K9F"
FT   HELIX           134..136
FT                   /evidence="ECO:0007829|PDB:3K9F"
FT   STRAND          141..143
FT                   /evidence="ECO:0007829|PDB:3K9F"
FT   STRAND          147..154
FT                   /evidence="ECO:0007829|PDB:3K9F"
FT   HELIX           161..165
FT                   /evidence="ECO:0007829|PDB:3K9F"
FT   STRAND          167..170
FT                   /evidence="ECO:0007829|PDB:3K9F"
FT   STRAND          175..178
FT                   /evidence="ECO:0007829|PDB:3K9F"
FT   HELIX           183..195
FT                   /evidence="ECO:0007829|PDB:3K9F"
FT   STRAND          196..198
FT                   /evidence="ECO:0007829|PDB:3KSB"
FT   HELIX           201..207
FT                   /evidence="ECO:0007829|PDB:3K9F"
FT   STRAND          218..220
FT                   /evidence="ECO:0007829|PDB:3K9F"
FT   HELIX           222..231
FT                   /evidence="ECO:0007829|PDB:3K9F"
FT   STRAND          232..239
FT                   /evidence="ECO:0007829|PDB:3K9F"
FT   STRAND          241..247
FT                   /evidence="ECO:0007829|PDB:3K9F"
FT   TURN            248..250
FT                   /evidence="ECO:0007829|PDB:3K9F"
FT   STRAND          251..258
FT                   /evidence="ECO:0007829|PDB:3K9F"
FT   HELIX           265..277
FT                   /evidence="ECO:0007829|PDB:3K9F"
FT   STRAND          280..283
FT                   /evidence="ECO:0007829|PDB:3K9F"
FT   STRAND          286..289
FT                   /evidence="ECO:0007829|PDB:3K9F"
FT   STRAND          298..301
FT                   /evidence="ECO:0007829|PDB:3K9F"
FT   HELIX           308..318
FT                   /evidence="ECO:0007829|PDB:3K9F"
FT   STRAND          322..328
FT                   /evidence="ECO:0007829|PDB:3K9F"
FT   STRAND          330..333
FT                   /evidence="ECO:0007829|PDB:3K9F"
FT   STRAND          336..339
FT                   /evidence="ECO:0007829|PDB:3K9F"
FT   HELIX           342..383
FT                   /evidence="ECO:0007829|PDB:3K9F"
FT   HELIX           385..394
FT                   /evidence="ECO:0007829|PDB:3K9F"
FT   STRAND          395..397
FT                   /evidence="ECO:0007829|PDB:3K9F"
FT   HELIX           398..409
FT                   /evidence="ECO:0007829|PDB:3K9F"
FT   HELIX           413..420
FT                   /evidence="ECO:0007829|PDB:3K9F"
FT   HELIX           424..428
FT                   /evidence="ECO:0007829|PDB:3K9F"
FT   HELIX           432..454
FT                   /evidence="ECO:0007829|PDB:3K9F"
FT   HELIX           456..474
FT                   /evidence="ECO:0007829|PDB:3K9F"
FT   STRAND          480..482
FT                   /evidence="ECO:0007829|PDB:3K9F"
SQ   SEQUENCE   823 AA;  93133 MW;  D4D17BD5DED63C05 CRC64;
     MSNIQNMSLE DIMGERFGRY SKYIIQDRAL PDIRDGLKPV QRRILYSMNK DSNTFDKSYR
     KSAKSVGNIM GNFHPHGDSS IYDAMVRMSQ NWKNREILVE MHGNNGSMDG DPPAAMRYTE
     ARLSEIAGYL LQDIEKKTVP FAWNFDDTEK EPTVLPAAFP NLLVNGSTGI SAGYATDIPP
     HNLAEVIDAA VYMIDHPTAK IDKLMEFLPG PDFPTGAIIQ GRDEIKKAYE TGKGRVVVRS
     KTEIEKLKGG KEQIVIIEIP YEINKANLVK KIDDVRVNNK VAGIAEVRDE SDRDGLRIAI
     ELKKDANTEL VLNYLFKYTD LQINYNFNMV AIDNFTPRQV GIVPILSSYI AHRREVILAR
     SRFDKEKAEK RLHIVEGLIR VISILDEVIA LIRASENKAD AKENLKVSYD FTEEQAEAIV
     TLQLYRLTNT DVVVLQEEEA ELREKIAMLA AIIGDERTMY NLMKKELREV KKKFATPRLS
     SLEDTAKAIE IDTASLIAEE DTYVSVTKAG YIKRTSPRSF AASTLEEIGK RDDDRLIFVQ
     SAKTTQHLLM FTSLGNVIYR PIHELADIRW KDIGEHLSQT ITNFETNEEI LYVEVLDQFD
     DATTYFAVTR LGQIKRVERK EFTPWRTYRS KSVKYAKLKD DTDQIVAVAP IKLDDVVLVS
     QNGYALRFNI EEVPVVGAKA AGVKAMNLKE DDVLQSGFIC NTSSFYLLTQ RGSLKRVSIE
     EILATSRAKR GLQVLRELKN KPHRVFLAGA VAEQGFVGDF FSTEVDVNDQ TLLVQSNKGT
     IYESRLQDLN LSERTSNGSF ISDTISDEEV FDAYLQEVVT EDK
//