PARC_STRPN
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 03-AUG-2022, entry version 158.
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}; OrderedLocusNames=SP_0855;
OS Streptococcus pneumoniae serotype 4 (strain ATCC BAA-334 / TIGR4).
OC Bacteria; Firmicutes; 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 STRING; 170187.SP_0855; -.
DR ChEMBL; CHEMBL2363033; -.
DR DrugBank; DB06771; Besifloxacin.
DR DrugBank; DB01044; Gatifloxacin.
DR DrugCentral; P72525; -.
DR PRIDE; P72525; -.
DR EnsemblBacteria; AAK74984; AAK74984; SP_0855.
DR KEGG; spn:SP_0855; -.
DR eggNOG; COG0188; Bacteria.
DR OMA; PRSNRID; -.
DR PhylomeDB; P72525; -.
DR BioCyc; SPNE170187:G1FZB-873-MON; -.
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; 1.10.268.10; -; 1.
DR Gene3D; 2.120.10.90; -; 1.
DR Gene3D; 3.90.199.10; -; 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 PANTHER; PTHR43493:SF9; PTHR43493:SF9; 1.
DR Pfam; PF03989; DNA_gyraseA_C; 5.
DR Pfam; PF00521; DNA_topoisoIV; 1.
DR SMART; SM00434; TOP4c; 1.
DR SUPFAM; SSF101904; SSF101904; 1.
DR SUPFAM; SSF56719; SSF56719; 1.
DR TIGRFAMs; TIGR01061; parC_Gpos; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cell membrane; DNA-binding; Isomerase; Membrane;
KW Topoisomerase.
FT CHAIN 1..823
FT /note="DNA topoisomerase 4 subunit A"
FT /id="PRO_0000145418"
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
