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-APR-2013, entry version 78.
DE RecName: Full=DNA topoisomerase 1;
DE EC=5.99.1.2;
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; dsDNA viruses, no RNA stage; Poxviridae; Chordopoxvirinae;
OC 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.,
RA Gashikov P.V., Belanov E.F., Belavin P.A., Resenchuk S.M.,
RA Andzhaparidze O.G., 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
RT distribution of sites in Poxvirus genomes.";
RL Virology 365:60-69(2007).
RN [4]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS), AND MUTAGENESIS OF 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).
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
CC transiently cleaving and rejoining one strand of the DNA duplex.
CC Introduces a single-strand break via transesterification at the
CC specific target site 5'-[CT]CCTTp site in duplex DNA. The scissile
CC phosphodiester is attacked by the catalytic tyrosine of the
CC enzyme, resulting in the formation of a DNA-(3'-phosphotyrosyl)-
CC enzyme intermediate and the expulsion of a 5'-OH DNA strand. The
CC free DNA strand then undergoes passage around the unbroken strand
CC thus removing DNA supercoils. Finally, in the religation step, the
CC DNA 5'-OH attacks the covalent intermediate to expel the active-
CC site tyrosine and restore the DNA phosphodiester backbone (By
CC similarity).
CC -!- CATALYTIC ACTIVITY: ATP-independent breakage of single-stranded
CC DNA, followed by passage and rejoining.
CC -!- INDUCTION: Expressed in the late phase of the viral replicative
CC cycle.
CC -!- SIMILARITY: Belongs to the type IB topoisomerase family.
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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 ProteinModelPortal; P32989; -.
DR SMR; P32989; 1-314.
DR GeneID; 1486444; -.
DR ProtClustDB; PHA3101; -.
DR EvolutionaryTrace; P32989; -.
DR GO; GO:0044383; C:host chromosome; IEA:InterPro.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0003917; F:DNA topoisomerase type I activity; IEA:EC.
DR GO; GO:0003918; F:DNA topoisomerase type II (ATP-hydrolyzing) activity; IEA:InterPro.
DR GO; GO:0006265; P:DNA topological change; IEA:InterPro.
DR Gene3D; 3.30.66.10; -; 1.
DR Gene3D; 3.90.15.10; -; 1.
DR InterPro; IPR011010; DNA_brk_join_enz.
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; SSF56349; DNA_brk_join_enz; 1.
DR PROSITE; PS00176; TOPOISOMERASE_I_EUK; 1.
PE 1: Evidence at protein level;
KW 3D-structure; ATP-binding; Complete proteome; DNA-binding; Isomerase;
KW Late protein; Nucleotide-binding; Reference proteome; Topoisomerase.
FT CHAIN 1 314 DNA topoisomerase 1.
FT /FTId=PRO_0000145217.
FT ACT_SITE 274 274 O-(3'-phospho-DNA)-tyrosine intermediate.
FT SITE 168 168 Involved in religation (Probable).
FT MUTAGEN 168 168 D->A: Increased DNA-binding affinity,
FT inhibition of product release, defective
FT in relaxation of supercoiled plasmid
FT substrates.
FT STRAND 3 7
FT STRAND 10 14
FT HELIX 27 33
FT STRAND 41 48
FT HELIX 50 53
FT STRAND 56 62
FT STRAND 68 72
FT HELIX 74 105
FT HELIX 113 127
FT HELIX 134 140
FT HELIX 150 152
FT STRAND 153 156
FT STRAND 159 165
FT HELIX 167 169
FT STRAND 171 177
FT HELIX 183 189
FT STRAND 197 200
FT HELIX 205 212
FT HELIX 213 215
FT HELIX 219 241
FT STRAND 242 244
FT HELIX 248 263
FT TURN 267 269
FT HELIX 270 273
FT HELIX 276 282
FT HELIX 288 293
FT HELIX 297 311
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
//
