TOP1_VAR67
ID TOP1_VAR67 Reviewed; 314 AA.
AC P32989;
DT 01-OCT-1993, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1993, sequence version 1.
DT 03-AUG-2022, entry version 117.
DE RecName: Full=DNA topoisomerase 1;
DE EC=5.6.2.1 {ECO:0000255|PROSITE-ProRule:PRU10130};
DE AltName: Full=DNA topoisomerase I;
GN Name=TOP1; ORFNames=H6R, I6R;
OS Variola virus (isolate Human/India/Ind3/1967) (VARV) (Smallpox virus).
OC Viruses; Varidnaviria; Bamfordvirae; Nucleocytoviricota; Pokkesviricetes;
OC Chitovirales; Poxviridae; Chordopoxvirinae; Orthopoxvirus.
OX NCBI_TaxID=587200;
OH NCBI_TaxID=9606; Homo sapiens (Human).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=8383392; DOI=10.1016/0168-1702(93)90110-9;
RA Shchelkunov S.N., Blinov V.M., Totmenin A.V., Marennikova S.S.,
RA Kolykhalov A.A., Frolov I.V., Chizhikov V.E., Gytorov V.V., Gashikov P.V.,
RA Belanov E.F., Belavin P.A., Resenchuk S.M., Andzhaparidze O.G.,
RA Sandakhchiev L.S.;
RT "Nucleotide sequence analysis of variola virus HindIII M, L, I genome
RT fragments.";
RL Virus Res. 27:25-35(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=8384129; DOI=10.1016/0014-5793(93)80041-r;
RA Shchelkunov S.N., Blinov V.M., Sandakhchiev L.S.;
RT "Genes of variola and vaccinia viruses necessary to overcome the host
RT protective mechanisms.";
RL FEBS Lett. 319:80-83(1993).
RN [3]
RP CHARACTERIZATION.
RX PubMed=17462694; DOI=10.1016/j.virol.2007.02.037;
RA Minkah N., Hwang Y., Perry K., Van Duyne G.D., Hendrickson R.,
RA Lefkowitz E.J., Hannenhalli S., Bushman F.D.;
RT "Variola virus topoisomerase: DNA cleavage specificity and distribution of
RT sites in Poxvirus genomes.";
RL Virology 365:60-69(2007).
RN [4]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS), ACTIVE SITE, AND MUTAGENESIS OF
RP ASP-168.
RX PubMed=16885024; DOI=10.1016/j.molcel.2006.06.015;
RA Perry K., Hwang Y., Bushman F.D., Van Duyne G.D.;
RT "Structural basis for specificity in the poxvirus topoisomerase.";
RL Mol. Cell 23:343-354(2006).
RN [5]
RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) IN COMPLEX WITH VANADATE.
RX PubMed=20152159; DOI=10.1016/j.str.2009.10.020;
RA Perry K., Hwang Y., Bushman F.D., Van Duyne G.D.;
RT "Insights from the structure of a smallpox virus topoisomerase-DNA
RT transition state mimic.";
RL Structure 18:127-137(2010).
CC -!- FUNCTION: Releases the supercoiling and torsional tension of DNA
CC introduced during the DNA replication and transcription by transiently
CC cleaving and rejoining one strand of the DNA duplex. Introduces a
CC single-strand break via transesterification at the specific target site
CC 5'-[CT]CCTTp site in duplex DNA. The scissile phosphodiester is
CC attacked by the catalytic tyrosine of the enzyme, resulting in the
CC formation of a DNA-(3'-phosphotyrosyl)-enzyme intermediate and the
CC expulsion of a 5'-OH DNA strand. The free DNA strand then undergoes
CC passage around the unbroken strand thus removing DNA supercoils.
CC Finally, in the religation step, the DNA 5'-OH attacks the covalent
CC intermediate to expel the active-site tyrosine and restore the DNA
CC phosphodiester backbone (By similarity). {ECO:0000250}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP-independent breakage of single-stranded DNA, followed by
CC passage and rejoining.; EC=5.6.2.1; Evidence={ECO:0000255|PROSITE-
CC ProRule:PRU10130};
CC -!- INDUCTION: Expressed in the late phase of the viral replicative cycle.
CC -!- SIMILARITY: Belongs to the type IB topoisomerase family. {ECO:0000305}.
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DR EMBL; X67119; CAA47588.1; -; Genomic_DNA.
DR EMBL; S55844; AAB24685.1; -; Genomic_DNA.
DR EMBL; X69198; CAA49030.1; -; Genomic_DNA.
DR PIR; E36846; E36846.
DR RefSeq; NP_042133.1; NC_001611.1.
DR PDB; 2H7F; X-ray; 2.70 A; X=1-314.
DR PDB; 2H7G; X-ray; 1.90 A; X=1-314.
DR PDB; 3IGC; X-ray; 2.10 A; A=1-314.
DR PDBsum; 2H7F; -.
DR PDBsum; 2H7G; -.
DR PDBsum; 3IGC; -.
DR SMR; P32989; -.
DR GeneID; 1486444; -.
DR KEGG; vg:1486444; -.
DR EvolutionaryTrace; P32989; -.
DR Proteomes; UP000002060; Genome.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0003917; F:DNA topoisomerase type I (single strand cut, ATP-independent) activity; IEA:UniProtKB-EC.
DR GO; GO:0006265; P:DNA topological change; IEA:InterPro.
DR CDD; cd00659; Topo_IB_C; 1.
DR Gene3D; 3.30.66.10; -; 1.
DR Gene3D; 3.90.15.10; -; 1.
DR InterPro; IPR011010; DNA_brk_join_enz.
DR InterPro; IPR035447; DNA_topo_I_N.
DR InterPro; IPR001631; TopoI.
DR InterPro; IPR018521; TopoI_AS.
DR InterPro; IPR014711; TopoI_cat_a-hlx-sub_euk.
DR InterPro; IPR013500; TopoI_cat_euk.
DR InterPro; IPR015346; TopoI_N_vir.
DR Pfam; PF01028; Topoisom_I; 1.
DR Pfam; PF09266; VirDNA-topo-I_N; 1.
DR PRINTS; PR00416; EUTPISMRASEI.
DR SUPFAM; SSF55869; SSF55869; 1.
DR SUPFAM; SSF56349; SSF56349; 1.
DR PROSITE; PS00176; TOPOISOMERASE_I_EUK; 1.
PE 1: Evidence at protein level;
KW 3D-structure; DNA-binding; Isomerase; Late protein; Reference proteome;
KW Topoisomerase.
FT CHAIN 1..314
FT /note="DNA topoisomerase 1"
FT /id="PRO_0000145217"
FT ACT_SITE 274
FT /note="O-(3'-phospho-DNA)-tyrosine intermediate"
FT /evidence="ECO:0000269|PubMed:16885024"
FT SITE 168
FT /note="Involved in religation"
FT /evidence="ECO:0000305|PubMed:16885024"
FT MUTAGEN 168
FT /note="D->A: Increased DNA-binding affinity, inhibition of
FT product release, defective in relaxation of supercoiled
FT plasmid substrates."
FT /evidence="ECO:0000269|PubMed:16885024"
FT STRAND 3..7
FT /evidence="ECO:0007829|PDB:2H7G"
FT STRAND 10..14
FT /evidence="ECO:0007829|PDB:2H7G"
FT HELIX 27..33
FT /evidence="ECO:0007829|PDB:2H7G"
FT STRAND 41..48
FT /evidence="ECO:0007829|PDB:2H7G"
FT HELIX 50..53
FT /evidence="ECO:0007829|PDB:2H7G"
FT STRAND 56..62
FT /evidence="ECO:0007829|PDB:2H7G"
FT STRAND 68..72
FT /evidence="ECO:0007829|PDB:2H7G"
FT HELIX 74..105
FT /evidence="ECO:0007829|PDB:2H7G"
FT HELIX 113..127
FT /evidence="ECO:0007829|PDB:2H7G"
FT HELIX 134..140
FT /evidence="ECO:0007829|PDB:2H7G"
FT HELIX 150..152
FT /evidence="ECO:0007829|PDB:2H7G"
FT STRAND 153..156
FT /evidence="ECO:0007829|PDB:2H7G"
FT STRAND 159..165
FT /evidence="ECO:0007829|PDB:2H7G"
FT HELIX 167..169
FT /evidence="ECO:0007829|PDB:2H7G"
FT STRAND 171..177
FT /evidence="ECO:0007829|PDB:2H7G"
FT HELIX 183..189
FT /evidence="ECO:0007829|PDB:2H7G"
FT STRAND 197..200
FT /evidence="ECO:0007829|PDB:2H7G"
FT HELIX 205..212
FT /evidence="ECO:0007829|PDB:2H7G"
FT HELIX 213..215
FT /evidence="ECO:0007829|PDB:2H7G"
FT HELIX 219..241
FT /evidence="ECO:0007829|PDB:2H7G"
FT STRAND 242..244
FT /evidence="ECO:0007829|PDB:2H7F"
FT HELIX 248..263
FT /evidence="ECO:0007829|PDB:2H7G"
FT TURN 267..269
FT /evidence="ECO:0007829|PDB:2H7G"
FT HELIX 270..273
FT /evidence="ECO:0007829|PDB:2H7G"
FT HELIX 276..282
FT /evidence="ECO:0007829|PDB:2H7G"
FT HELIX 288..293
FT /evidence="ECO:0007829|PDB:2H7G"
FT HELIX 297..311
FT /evidence="ECO:0007829|PDB:2H7G"
SQ SEQUENCE 314 AA; 36592 MW; AE9C7DC5FA363BEE CRC64;
MRALFYKDGK LFTDNNFLNP VSDNNPAYEV LQHVKIPTHL TDVVVYGQTW EEALTRLIFV
GSDSKGRRQY FYGKMHVQNR NAKRDRIFVR VYNVMKRINC FINKNIKKSS TDSNYQLAVF
MLMETMFFIR FGKMKYLKEN ETVGLLTLKN KHIEISPDKI VIKFVGKDKV SHEFVVHKSN
RLYKPLLKLT DDSSPEEFLF NKLSERKVYE CIKQFGIRIK DLRTYGVNYT FLYNFWTNVK
SISPLPSPKK LIALTIKQTA EVVGHTPSIS KRAYMATTIL EMVKDKNFLD VVSKTTFDEF
LSIVVDHVKS STDG
