TOP1_MYCTU
ID TOP1_MYCTU Reviewed; 934 AA.
AC P9WG49; L0TDE3; O08383; P0A620; Q59567;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 50.
DE RecName: Full=DNA topoisomerase 1 {ECO:0000255|HAMAP-Rule:MF_00952};
DE EC=5.6.2.1 {ECO:0000255|HAMAP-Rule:MF_00952};
DE AltName: Full=DNA topoisomerase I {ECO:0000255|HAMAP-Rule:MF_00952};
DE AltName: Full=Omega-protein;
DE AltName: Full=Relaxing enzyme;
DE AltName: Full=Swivelase;
DE AltName: Full=Untwisting enzyme;
GN Name=topA {ECO:0000255|HAMAP-Rule:MF_00952}; OrderedLocusNames=Rv3646c;
GN ORFNames=MTCY15C10.06;
OS Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv).
OC Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae;
OC Mycobacterium; Mycobacterium tuberculosis complex.
OX NCBI_TaxID=83332;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=9634230; DOI=10.1038/31159;
RA Cole S.T., Brosch R., Parkhill J., Garnier T., Churcher C.M., Harris D.E.,
RA Gordon S.V., Eiglmeier K., Gas S., Barry C.E. III, Tekaia F., Badcock K.,
RA Basham D., Brown D., Chillingworth T., Connor R., Davies R.M., Devlin K.,
RA Feltwell T., Gentles S., Hamlin N., Holroyd S., Hornsby T., Jagels K.,
RA Krogh A., McLean J., Moule S., Murphy L.D., Oliver S., Osborne J.,
RA Quail M.A., Rajandream M.A., Rogers J., Rutter S., Seeger K., Skelton S.,
RA Squares S., Squares R., Sulston J.E., Taylor K., Whitehead S.,
RA Barrell B.G.;
RT "Deciphering the biology of Mycobacterium tuberculosis from the complete
RT genome sequence.";
RL Nature 393:537-544(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-895, AND FUNCTION.
RC STRAIN=ATCC 35801 / TMC 107 / Erdman;
RX PubMed=8921893; DOI=10.1016/0378-1119(96)00335-6;
RA Yang F.D., Lu G., Rubin H.;
RT "Cloning, expression, purification and characterization of DNA
RT topoisomerase I of Mycobacterium tuberculosis.";
RL Gene 178:63-69(1996).
RN [3]
RP IDENTIFICATION AS A DRUG TARGET [LARGE SCALE ANALYSIS].
RX PubMed=19099550; DOI=10.1186/1752-0509-2-109;
RA Raman K., Yeturu K., Chandra N.;
RT "targetTB: a target identification pipeline for Mycobacterium tuberculosis
RT through an interactome, reactome and genome-scale structural analysis.";
RL BMC Syst. Biol. 2:109-109(2008).
RN [4]
RP FUNCTION AS A TOPOISOMERASE, DNA CLEAVAGE, SSDNA-BINDING, INTERACTION WITH
RP MAZF4, INHIBITION BY MAZF4, INHIBITION OF MAZF ACTIVITY, AND ACTIVITY
RP REGULATION.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=20724443; DOI=10.1093/nar/gkq737;
RA Huang F., He Z.G.;
RT "Characterization of an interplay between a Mycobacterium tuberculosis MazF
RT homolog, Rv1495 and its sole DNA topoisomerase I.";
RL Nucleic Acids Res. 38:8219-8230(2010).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=21969609; DOI=10.1074/mcp.m111.011627;
RA Kelkar D.S., Kumar D., Kumar P., Balakrishnan L., Muthusamy B., Yadav A.K.,
RA Shrivastava P., Marimuthu A., Anand S., Sundaram H., Kingsbury R.,
RA Harsha H.C., Nair B., Prasad T.S., Chauhan D.S., Katoch K., Katoch V.M.,
RA Kumar P., Chaerkady R., Ramachandran S., Dash D., Pandey A.;
RT "Proteogenomic analysis of Mycobacterium tuberculosis by high resolution
RT mass spectrometry.";
RL Mol. Cell. Proteomics 10:M111.011627-M111.011627(2011).
CC -!- FUNCTION: Releases the supercoiling and torsional tension of DNA, which
CC is introduced during the DNA replication and transcription, by
CC transiently cleaving and rejoining one strand of the DNA duplex
CC (PubMed:8921893, PubMed:20724443). Introduces a single-strand break via
CC transesterification at a target site in duplex DNA. The scissile
CC phosphodiester is attacked by the catalytic tyrosine of the enzyme,
CC resulting in the formation of a DNA-(5'-phosphotyrosyl)-enzyme
CC intermediate and the expulsion of a 3'-OH DNA strand. The free DNA
CC strand then undergoes passage around the unbroken strand, thus removing
CC DNA supercoils. Finally, in the religation step, the DNA 3'-OH attacks
CC the covalent intermediate to expel the active-site tyrosine and restore
CC the DNA phosphodiester backbone. {ECO:0000255|HAMAP-Rule:MF_00952,
CC ECO:0000269|PubMed:20724443, ECO:0000269|PubMed:8921893}.
CC -!- FUNCTION: The C-terminus (residues 622-934) inhibits RNA cleavage by
CC MazF4. {ECO:0000269|PubMed:20724443}.
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|HAMAP-
CC Rule:MF_00952};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_00952};
CC Note=Binds two Mg(2+) per subunit. {ECO:0000255|HAMAP-Rule:MF_00952};
CC -!- ACTIVITY REGULATION: SsDNA cleavage is inhibited by MazF4.
CC {ECO:0000269|PubMed:20724443}.
CC -!- SUBUNIT: Monomer (By similarity). Interacts with mRNA interferase
CC MazF4. {ECO:0000255|HAMAP-Rule:MF_00952, ECO:0000269|PubMed:20724443}.
CC -!- MISCELLANEOUS: Was identified as a high-confidence drug target.
CC -!- SIMILARITY: Belongs to the type IA topoisomerase family.
CC {ECO:0000255|HAMAP-Rule:MF_00952}.
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DR EMBL; AL123456; CCP46469.1; -; Genomic_DNA.
DR EMBL; U40159; AAC44599.1; -; Genomic_DNA.
DR PIR; G70563; G70563.
DR RefSeq; NP_218163.1; NC_000962.3.
DR RefSeq; WP_003899617.1; NZ_NVQJ01000045.1.
DR PDB; 5D5H; X-ray; 2.52 A; A=2-704.
DR PDB; 5UJ1; X-ray; 2.15 A; A=2-704.
DR PDB; 5UJY; X-ray; 2.70 A; A/B=2-704.
DR PDB; 6CQ2; X-ray; 3.00 A; A=2-704.
DR PDB; 6CQI; X-ray; 2.42 A; A=2-704.
DR PDBsum; 5D5H; -.
DR PDBsum; 5UJ1; -.
DR PDBsum; 5UJY; -.
DR PDBsum; 6CQ2; -.
DR PDBsum; 6CQI; -.
DR AlphaFoldDB; P9WG49; -.
DR SMR; P9WG49; -.
DR STRING; 83332.Rv3646c; -.
DR PaxDb; P9WG49; -.
DR PRIDE; P9WG49; -.
DR DNASU; 885608; -.
DR GeneID; 45427643; -.
DR GeneID; 885608; -.
DR KEGG; mtu:Rv3646c; -.
DR TubercuList; Rv3646c; -.
DR eggNOG; COG0550; Bacteria.
DR eggNOG; COG1754; Bacteria.
DR OMA; YAQPKQR; -.
DR PhylomeDB; P9WG49; -.
DR BRENDA; 5.6.2.1; 3445.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005829; C:cytosol; HDA:MTBBASE.
DR GO; GO:0009274; C:peptidoglycan-based cell wall; HDA:MTBBASE.
DR GO; GO:0005886; C:plasma membrane; HDA:MTBBASE.
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; IDA:MTBBASE.
DR GO; GO:0000287; F:magnesium ion binding; IDA:MTBBASE.
DR GO; GO:0006265; P:DNA topological change; IEA:UniProtKB-UniRule.
DR GO; GO:0060701; P:negative regulation of ribonuclease activity; IDA:MTBBASE.
DR CDD; cd00186; TOP1Ac; 1.
DR CDD; cd03363; TOPRIM_TopoIA_TopoI; 1.
DR Gene3D; 1.10.290.10; -; 1.
DR Gene3D; 1.10.460.10; -; 1.
DR Gene3D; 2.70.20.10; -; 1.
DR HAMAP; MF_00952; Topoisom_1_prok; 1.
DR InterPro; IPR000380; Topo_IA.
DR InterPro; IPR003601; Topo_IA_2.
DR InterPro; IPR023406; Topo_IA_AS.
DR InterPro; IPR013497; Topo_IA_cen.
DR InterPro; IPR013824; Topo_IA_cen_sub1.
DR InterPro; IPR013825; Topo_IA_cen_sub2.
DR InterPro; IPR013826; Topo_IA_cen_sub3.
DR InterPro; IPR023405; Topo_IA_core_domain.
DR InterPro; IPR003602; Topo_IA_DNA-bd_dom.
DR InterPro; IPR005733; TopoI_bac-type.
DR InterPro; IPR028612; Topoisom_1_IA.
DR InterPro; IPR025589; Toprim_C_rpt.
DR InterPro; IPR006171; TOPRIM_domain.
DR InterPro; IPR034149; TOPRIM_TopoI.
DR PANTHER; PTHR42785; PTHR42785; 2.
DR Pfam; PF01131; Topoisom_bac; 1.
DR Pfam; PF01751; Toprim; 1.
DR Pfam; PF13368; Toprim_C_rpt; 4.
DR PRINTS; PR00417; PRTPISMRASEI.
DR SMART; SM00437; TOP1Ac; 1.
DR SMART; SM00436; TOP1Bc; 1.
DR SMART; SM00493; TOPRIM; 1.
DR SUPFAM; SSF56712; SSF56712; 1.
DR TIGRFAMs; TIGR01051; topA_bact; 1.
DR PROSITE; PS00396; TOPOISOMERASE_I_PROK; 1.
DR PROSITE; PS50880; TOPRIM; 1.
PE 1: Evidence at protein level;
KW 3D-structure; DNA-binding; Isomerase; Magnesium; Metal-binding;
KW Reference proteome; Topoisomerase.
FT CHAIN 1..934
FT /note="DNA topoisomerase 1"
FT /id="PRO_0000145159"
FT DOMAIN 18..142
FT /note="Toprim"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00952"
FT REGION 1..20
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 191..196
FT /note="Interaction with DNA"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00952"
FT REGION 746..765
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 842..892
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 905..934
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 913..934
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 342
FT /note="O-(5'-phospho-DNA)-tyrosine intermediate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00952"
FT BINDING 24
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00952"
FT BINDING 111
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00952"
FT BINDING 111
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00952"
FT BINDING 113
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00952"
FT SITE 48
FT /note="Interaction with DNA"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00952"
FT SITE 167
FT /note="Interaction with DNA"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00952"
FT SITE 168
FT /note="Interaction with DNA"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00952"
FT SITE 171
FT /note="Interaction with DNA"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00952"
FT SITE 176
FT /note="Interaction with DNA"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00952"
FT SITE 183
FT /note="Interaction with DNA"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00952"
FT SITE 344
FT /note="Interaction with DNA"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00952"
FT SITE 547
FT /note="Interaction with DNA"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00952"
FT CONFLICT 1
FT /note="M -> MERGAQL (in Ref. 2; AAC44599)"
FT /evidence="ECO:0000305"
FT CONFLICT 53..61
FT /note="PRAASDVPA -> RGPRRCTR (in Ref. 2; AAC44599)"
FT /evidence="ECO:0000305"
FT CONFLICT 255..281
FT /note="RDFDSLGTLRKGDEVIVLDEGSATALA -> AISTRWARCAKATKSLCSTRG
FT ARPRWP (in Ref. 2; AAC44599)"
FT /evidence="ECO:0000305"
FT CONFLICT 369..372
FT /note="EYVA -> GVRR (in Ref. 2; AAC44599)"
FT /evidence="ECO:0000305"
FT CONFLICT 797
FT /note="G -> V (in Ref. 2; AAC44599)"
FT /evidence="ECO:0000305"
FT CONFLICT 853..895
FT /note="PLRELGTDPASGKPMVIKDGRFGPYVTDGETNASLRKGDDVAS -> ACASW
FT EQIRRRASQWSSRTADSGRTSPTVRPMPACVRATTWLP (in Ref. 2;
FT AAC44599)"
FT /evidence="ECO:0000305"
FT STRAND 19..24
FT /evidence="ECO:0007829|PDB:5UJ1"
FT HELIX 26..36
FT /evidence="ECO:0007829|PDB:5UJ1"
FT STRAND 40..44
FT /evidence="ECO:0007829|PDB:5UJ1"
FT STRAND 49..52
FT /evidence="ECO:0007829|PDB:5UJ1"
FT HELIX 56..58
FT /evidence="ECO:0007829|PDB:5UJ1"
FT HELIX 61..63
FT /evidence="ECO:0007829|PDB:5UJ1"
FT TURN 67..72
FT /evidence="ECO:0007829|PDB:5UJ1"
FT TURN 75..79
FT /evidence="ECO:0007829|PDB:5UJ1"
FT HELIX 87..89
FT /evidence="ECO:0007829|PDB:5UJ1"
FT HELIX 90..100
FT /evidence="ECO:0007829|PDB:5UJ1"
FT STRAND 104..108
FT /evidence="ECO:0007829|PDB:5UJ1"
FT HELIX 114..127
FT /evidence="ECO:0007829|PDB:5UJ1"
FT STRAND 133..135
FT /evidence="ECO:0007829|PDB:5UJ1"
FT STRAND 140..142
FT /evidence="ECO:0007829|PDB:6CQI"
FT HELIX 143..151
FT /evidence="ECO:0007829|PDB:5UJ1"
FT HELIX 158..185
FT /evidence="ECO:0007829|PDB:5UJ1"
FT HELIX 194..212
FT /evidence="ECO:0007829|PDB:5UJ1"
FT STRAND 217..226
FT /evidence="ECO:0007829|PDB:5UJ1"
FT TURN 228..230
FT /evidence="ECO:0007829|PDB:5UJ1"
FT STRAND 235..246
FT /evidence="ECO:0007829|PDB:5UJ1"
FT STRAND 249..251
FT /evidence="ECO:0007829|PDB:5UJ1"
FT HELIX 254..256
FT /evidence="ECO:0007829|PDB:5UJ1"
FT STRAND 261..263
FT /evidence="ECO:0007829|PDB:5UJ1"
FT STRAND 265..267
FT /evidence="ECO:0007829|PDB:5UJ1"
FT HELIX 274..282
FT /evidence="ECO:0007829|PDB:5UJ1"
FT TURN 283..286
FT /evidence="ECO:0007829|PDB:5UJ1"
FT STRAND 287..301
FT /evidence="ECO:0007829|PDB:5UJ1"
FT HELIX 309..320
FT /evidence="ECO:0007829|PDB:5UJ1"
FT HELIX 324..336
FT /evidence="ECO:0007829|PDB:5UJ1"
FT STRAND 339..341
FT /evidence="ECO:0007829|PDB:5UJ1"
FT HELIX 352..366
FT /evidence="ECO:0007829|PDB:5UJ1"
FT HELIX 368..370
FT /evidence="ECO:0007829|PDB:5UJ1"
FT TURN 385..387
FT /evidence="ECO:0007829|PDB:5UJ1"
FT TURN 396..399
FT /evidence="ECO:0007829|PDB:5UJ1"
FT HELIX 402..408
FT /evidence="ECO:0007829|PDB:5UJ1"
FT HELIX 411..413
FT /evidence="ECO:0007829|PDB:5UJ1"
FT HELIX 414..429
FT /evidence="ECO:0007829|PDB:5UJ1"
FT STRAND 435..448
FT /evidence="ECO:0007829|PDB:5UJ1"
FT STRAND 451..460
FT /evidence="ECO:0007829|PDB:5UJ1"
FT HELIX 466..469
FT /evidence="ECO:0007829|PDB:5UJ1"
FT TURN 477..479
FT /evidence="ECO:0007829|PDB:5UJ1"
FT STRAND 498..510
FT /evidence="ECO:0007829|PDB:5UJ1"
FT HELIX 519..528
FT /evidence="ECO:0007829|PDB:5UJ1"
FT TURN 534..536
FT /evidence="ECO:0007829|PDB:5UJ1"
FT HELIX 537..546
FT /evidence="ECO:0007829|PDB:5UJ1"
FT STRAND 549..553
FT /evidence="ECO:0007829|PDB:5UJ1"
FT STRAND 556..559
FT /evidence="ECO:0007829|PDB:5UJ1"
FT HELIX 561..573
FT /evidence="ECO:0007829|PDB:5UJ1"
FT HELIX 575..578
FT /evidence="ECO:0007829|PDB:5UJ1"
FT HELIX 580..594
FT /evidence="ECO:0007829|PDB:5UJ1"
FT STRAND 596..598
FT /evidence="ECO:0007829|PDB:6CQ2"
FT HELIX 600..609
FT /evidence="ECO:0007829|PDB:5UJ1"
FT HELIX 620..622
FT /evidence="ECO:0007829|PDB:5UJ1"
FT HELIX 625..629
FT /evidence="ECO:0007829|PDB:5UJ1"
FT HELIX 633..635
FT /evidence="ECO:0007829|PDB:5UJ1"
FT HELIX 638..641
FT /evidence="ECO:0007829|PDB:5UJ1"
FT STRAND 643..648
FT /evidence="ECO:0007829|PDB:5UJ1"
FT STRAND 654..660
FT /evidence="ECO:0007829|PDB:5UJ1"
FT STRAND 663..672
FT /evidence="ECO:0007829|PDB:5UJ1"
FT STRAND 675..683
FT /evidence="ECO:0007829|PDB:5UJ1"
FT HELIX 690..692
FT /evidence="ECO:0007829|PDB:5UJ1"
FT HELIX 695..703
FT /evidence="ECO:0007829|PDB:5UJ1"
SQ SEQUENCE 934 AA; 102336 MW; B29E2C17897781BA CRC64;
MADPKTKGRG SGGNGSGRRL VIVESPTKAR KLASYLGSGY IVESSRGHIR DLPRAASDVP
AKYKSQPWAR LGVNVDADFE PLYIISPEKR STVSELRGLL KDVDELYLAT DGDREGEAIA
WHLLETLKPR IPVKRMVFHE ITEPAIRAAA EHPRDLDIDL VDAQETRRIL DRLYGYEVSP
VLWKKVAPKL SAGRVQSVAT RIIVARERDR MAFRSAAYWD ILAKLDASVS DPDAAPPTFS
ARLTAVAGRR VATGRDFDSL GTLRKGDEVI VLDEGSATAL AAGLDGTQLT VASAEEKPYA
RRPYPPFMTS TLQQEASRKL RFSAERTMSI AQRLYENGYI TYMRTDSTTL SESAINAART
QARQLYGDEY VAPAPRQYTR KVKNAQEAHE AIRPAGETFA TPDAVRRELD GPNIDDFRLY
ELIWQRTVAS QMADARGMTL SLRITGMSGH QEVVFSATGR TLTFPGFLKA YVETVDELVG
GEADDAERRL PHLTPGQRLD IVELTPDGHA TNPPARYTEA SLVKALEELG IGRPSTYSSI
IKTIQDRGYV HKKGSALVPS WVAFAVTGLL EQHFGRLVDY DFTAAMEDEL DEIAAGNERR
TNWLNNFYFG GDHGVPDSVA RSGGLKKLVG INLEGIDARE VNSIKLFDDT HGRPIYVRVG
KNGPYLERLV AGDTGEPTPQ RANLSDSITP DELTLQVAEE LFATPQQGRT LGLDPETGHE
IVAREGRFGP YVTEILPEPA ADAAAAAQGV KKRQKAAGPK PRTGSLLRSM DLQTVTLEDA
LRLLSLPRVV GVDPASGEEI TAQNGRYGPY LKRGNDSRSL VTEDQIFTIT LDEALKIYAE
PKRRGRQSAS APPLRELGTD PASGKPMVIK DGRFGPYVTD GETNASLRKG DDVASITDER
AAELLADRRA RGPAKRPARK AARKVPAKKA AKRD
