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 02-SEP-2026, entry version 127. 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=OPG111; Synonyms=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; OC Orthopoxvirus variola; Variola virus. 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. {ECO:0000250|UniProtKB:P68698}. 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 -!- SUBCELLULAR LOCATION: Virion {ECO:0000250|UniProtKB:P68698}. CC -!- INDUCTION: Expressed in the late phase of the viral replicative cycle. CC -!- SIMILARITY: Belongs to the type IB topoisomerase family. {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; 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 AlphaFoldDB; P32989; -. DR SMR; P32989; -. DR GeneID; 1486444; -. DR KEGG; vg:1486444; -. DR EvolutionaryTrace; P32989; -. DR Proteomes; UP000002060; Segment. 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; DNA topoisomerase I domain; 1. DR Gene3D; 3.90.15.10; Topoisomerase I, Chain A, domain 3; 1. DR InterPro; IPR011010; DNA_brk_join_enz. DR InterPro; IPR035447; DNA_topo_I_N_sf. DR InterPro; IPR001631; TopoI. DR InterPro; IPR014711; TopoI_cat_a-hlx-sub_euk. DR InterPro; IPR013500; TopoI_cat_euk. DR InterPro; IPR015346; TopoI_N_vir. DR InterPro; IPR018521; TopoIB_AS. DR Pfam; PF01028; Topoisom_I; 1. DR Pfam; PF09266; VirDNA-topo-I_N; 1. DR PRINTS; PR00416; EUTPISMRASEI. DR SUPFAM; SSF56349; DNA breaking-rejoining enzymes; 1. DR SUPFAM; SSF55869; DNA topoisomerase I domain; 1. DR PROSITE; PS00176; TOPO_IB_1; 1. DR PROSITE; PS52038; TOPO_IB_2; 1. DR PDBsum; 2H7F; -. DR PDBsum; 2H7G; -. DR PDBsum; 3IGC; -. PE 1: Evidence at protein level; KW 3D-structure; DNA-binding; Isomerase; Late protein; Reference proteome; KW Topoisomerase; Virion. FT CHAIN 1..314 FT /note="DNA topoisomerase 1" FT /id="PRO_0000145217" FT DOMAIN 77..314 FT /note="Topo IB-type catalytic" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01382" FT ACT_SITE 274 FT /note="O-(3'-phospho-DNA)-tyrosine intermediate" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01382, FT 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 HELIX 35..37 FT /evidence="ECO:0007829|PDB:3IGC" 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 245..247 FT /evidence="ECO:0007829|PDB:2H7G" 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 //