ID GYRA_MYCTU Reviewed; 838 AA. AC P9WG47; J9VB15; P71574; P97136; Q07702; DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot. DT 16-APR-2014, sequence version 1. DT 24-JAN-2024, entry version 64. DE RecName: Full=DNA gyrase subunit A {ECO:0000255|HAMAP-Rule:MF_01897}; DE EC=5.6.2.2 {ECO:0000255|HAMAP-Rule:MF_01897, ECO:0000269|PubMed:15047530, ECO:0000269|PubMed:16876125}; DE AltName: Full=Type IIA topoisomerase subunit GyrA; GN Name=gyrA {ECO:0000255|HAMAP-Rule:MF_01897}; OrderedLocusNames=Rv0006; GN ORFNames=MTCY10H4.04; OS Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv). OC Bacteria; Actinomycetota; Actinomycetes; Mycobacteriales; Mycobacteriaceae; OC Mycobacterium; Mycobacterium tuberculosis complex. OX NCBI_TaxID=83332; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS VAL-90; PRO-91; ALA-94; GLY-94; RP HIS-94; ASN-94 AND TYR-94, MUTAGENESIS OF GLY-88, AND ANTIBIOTIC RP RESISTANCE. RC STRAIN=ATCC 25618 / H37Rv; RX PubMed=8031045; DOI=10.1128/aac.38.4.773; RA Takiff H.E., Salazar L., Guerrero C., Philipp W., Huang W.M., RA Kreiswirth B., Cole S.T., Jacobs W.R. Jr., Telenti A.; RT "Cloning and nucleotide sequence of Mycobacterium tuberculosis gyrA and RT gyrB genes and detection of quinolone resistance mutations."; RL Antimicrob. Agents Chemother. 38:773-780(1994). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RC STRAIN=2997164; RX PubMed=22972833; DOI=10.1128/jcm.01893-12; RA Daum L.T., Rodriguez J.D., Worthy S.A., Ismail N.A., Omar S.V., RA Dreyer A.W., Fourie P.B., Hoosen A.A., Chambers J.P., Fischer G.W.; RT "Next-generation ion torrent sequencing of drug resistance mutations in RT Mycobacterium tuberculosis strains."; RL J. Clin. Microbiol. 50:3831-3837(2012). RN [3] 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 [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 82-188. RC STRAIN=ATCC 25618 / H37Rv; RX PubMed=8294019; DOI=10.1016/0378-1119(93)90481-h; RA Mizrahi V., Huberts P., Dawes S.S., Dudding L.R.; RT "A PCR method for the sequence analysis of the gyrA, polA and rnhA gene RT segments from mycobacteria."; RL Gene 136:287-290(1993). RN [5] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 89-124, MUTAGENESIS OF ASP-94, AND RP ANTIBIOTIC RESISTANCE. RC STRAIN=ATCC 25618 / H37Rv; RX PubMed=8035042; DOI=10.1093/infdis/170.2.479; RA Cambau E., Sougakoff W., Besson M., Truffot-Pernot C., Grosset J., RA Jarlier V.; RT "Selection of a gyrA mutant of Mycobacterium tuberculosis resistant to RT fluoroquinolones during treatment with ofloxacin."; RL J. Infect. Dis. 170:479-483(1994). RN [6] RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, SUBUNIT, AND REACTION RP MECHANISM. RC STRAIN=ATCC 25618 / H37Rv; RX PubMed=15047530; DOI=10.1128/aac.48.4.1281-1288.2004; RA Aubry A., Pan X.S., Fisher L.M., Jarlier V., Cambau E.; RT "Mycobacterium tuberculosis DNA gyrase: interaction with quinolones and RT correlation with antimycobacterial drug activity."; RL Antimicrob. Agents Chemother. 48:1281-1288(2004). RN [7] RP FUNCTION, MUTAGENESIS OF THR-80; ALA-90 AND ASP-94, AND ANTIBIOTIC RP RESISTANCE. RC STRAIN=H37Rv; RX PubMed=16377674; DOI=10.1128/aac.50.1.104-112.2006; RA Aubry A., Veziris N., Cambau E., Truffot-Pernot C., Jarlier V., RA Fisher L.M.; RT "Novel gyrase mutations in quinolone-resistant and -hypersusceptible RT clinical isolates of Mycobacterium tuberculosis: functional analysis of RT mutant enzymes."; RL Antimicrob. Agents Chemother. 50:104-112(2006). RN [8] RP FUNCTION, CATALYTIC ACTIVITY, AND ACTIVITY REGULATION. RC STRAIN=H37Rv; RX PubMed=16876125; DOI=10.1016/j.bbrc.2006.07.017; RA Aubry A., Fisher L.M., Jarlier V., Cambau E.; RT "First functional characterization of a singly expressed bacterial type II RT topoisomerase: the enzyme from Mycobacterium tuberculosis."; RL Biochem. Biophys. Res. Commun. 348:158-165(2006). RN [9] RP FUNCTION, ACTIVITY REGULATION, MUTAGENESIS OF GLY-88, AND RP ANTIBIOTIC-RESISTANCE. RC STRAIN=H37Rv; RX PubMed=17015625; DOI=10.1128/aac.00944-06; RA Matrat S., Veziris N., Mayer C., Jarlier V., Truffot-Pernot C., Camuset J., RA Bouvet E., Cambau E., Aubry A.; RT "Functional analysis of DNA gyrase mutant enzymes carrying mutations at RT position 88 in the A subunit found in clinical strains of Mycobacterium RT tuberculosis resistant to fluoroquinolones."; RL Antimicrob. Agents Chemother. 50:4170-4173(2006). RN [10] RP FUNCTION, MUTAGENESIS OF ALA-90, AND ANTIBIOTIC SUSCEPTIBILITY. RX PubMed=18426901; DOI=10.1128/aac.01380-07; RA Matrat S., Aubry A., Mayer C., Jarlier V., Cambau E.; RT "Mutagenesis in the alpha3alpha4 GyrA helix and in the Toprim domain of RT GyrB refines the contribution of Mycobacterium tuberculosis DNA gyrase to RT intrinsic resistance to quinolones."; RL Antimicrob. Agents Chemother. 52:2909-2914(2008). RN [11] RP FUNCTION, ACTIVITY REGULATION, AND MUTAGENESIS OF ALA-90 AND ASP-94. RC STRAIN=H37Rv; RX PubMed=19060136; DOI=10.1128/jb.01205-08; RA Merens A., Matrat S., Aubry A., Lascols C., Jarlier V., Soussy C.J., RA Cavallo J.D., Cambau E.; RT "The pentapeptide repeat proteins MfpAMt and QnrB4 exhibit opposite effects RT on DNA gyrase catalytic reactions and on the ternary gyrase-DNA-quinolone RT complex."; RL J. Bacteriol. 191:1587-1594(2009). RN [12] RP ACETYLATION [LARGE SCALE ANALYSIS] AT THR-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. RC STRAIN=ATCC 25618 / H37Rv; RX PubMed=21969609; DOI=10.1074/mcp.m111.011445; 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). RN [13] RP FUNCTION, POSSIBLE CALCIUM COFACTOR, POSSIBLE EF-HAND DOMAIN, AND RP MUTAGENESIS OF 504-ASP--ASP-514 AND 508-GLU-ASP-509. RX PubMed=22844097; DOI=10.1093/nar/gks704; RA Karkare S., Yousafzai F., Mitchenall L.A., Maxwell A.; RT "The role of Ca(2+) in the activity of Mycobacterium tuberculosis DNA RT gyrase."; RL Nucleic Acids Res. 40:9774-9787(2012). RN [14] RP ACTIVITY REGULATION. RC STRAIN=H37Rv; RX PubMed=23268609; DOI=10.1021/cb300510w; RA Shirude P.S., Madhavapeddi P., Tucker J.A., Murugan K., Patil V., RA Basavarajappa H., Raichurkar A.V., Humnabadkar V., Hussein S., Sharma S., RA Ramya V.K., Narayan C.B., Balganesh T.S., Sambandamurthy V.K.; RT "Aminopyrazinamides: novel and specific GyrB inhibitors that kill RT replicating and nonreplicating Mycobacterium tuberculosis."; RL ACS Chem. Biol. 8:519-523(2013). RN [15] RP ACTIVITY REGULATION. RC STRAIN=ATCC 27294 / TMC 102 / H37Rv; RX PubMed=24126580; DOI=10.1128/aac.01751-13; RA P S.H., Solapure S., Mukherjee K., Nandi V., Waterson D., Shandil R., RA Balganesh M., Sambandamurthy V.K., Raichurkar A.K., Deshpande A., Ghosh A., RA Awasthy D., Shanbhag G., Sheikh G., McMiken H., Puttur J., Reddy J., RA Werngren J., Read J., Kumar M., R M., Chinnapattu M., Madhavapeddi P., RA Manjrekar P., Basu R., Gaonkar S., Sharma S., Hoffner S., Humnabadkar V., RA Subbulakshmi V., Panduga V.; RT "Optimization of pyrrolamides as mycobacterial GyrB ATPase inhibitors: RT structure-activity relationship and in vivo efficacy in a mouse model of RT tuberculosis."; RL Antimicrob. Agents Chemother. 58:61-70(2014). RN [16] RP X-RAY CRYSTALLOGRAPHY (1.60 ANGSTROMS) OF 34-500. RX PubMed=19787774; DOI=10.1002/prot.22600; RA Tretter E.M., Schoeffler A.J., Weisfield S.R., Berger J.M.; RT "Crystal structure of the DNA gyrase GyrA N-terminal domain from RT Mycobacterium tuberculosis."; RL Proteins 78:492-495(2010). RN [17] RP X-RAY CRYSTALLOGRAPHY (2.70 ANGSTROMS) OF 1-501, FUNCTION, AND DOMAIN. RX PubMed=20805881; DOI=10.1371/journal.pone.0012245; RA Piton J., Petrella S., Delarue M., Andre-Leroux G., Jarlier V., Aubry A., RA Mayer C.; RT "Structural insights into the quinolone resistance mechanism of RT Mycobacterium tuberculosis DNA gyrase."; RL PLoS ONE 5:E12245-E12245(2010). RN [18] RP X-RAY CRYSTALLOGRAPHY (1.65 ANGSTROMS) OF 514-838, FUNCTION, DOMAIN, AND RP DNA-BINDING. RC STRAIN=ATCC 25618 / H37Rv; RX PubMed=22457352; DOI=10.1074/jbc.m112.345736; RA Tretter E.M., Berger J.M.; RT "Mechanisms for defining supercoiling set point of DNA gyrase orthologs: RT II. The shape of the GyrA subunit C-terminal domain (CTD) is not a sole RT determinant for controlling supercoiling efficiency."; RL J. Biol. Chem. 287:18645-18654(2012). RN [19] RP X-RAY CRYSTALLOGRAPHY (1.40 ANGSTROMS) OF 512-838, FUNCTION, DOMAIN, RP DNA-BINDING, AND MUTAGENESIS OF LYS-538; 540-GLY--GLY-543; GLY-540; RP GLY-541; GLY-543; 544-VAL-GLN-545; 746-GLY--GLY-749; GLY-747; GLY-749 AND RP GLY-749. RC STRAIN=H37Rv; RX PubMed=23869946; DOI=10.1042/bj20130430; RA Bouige A., Darmon A., Piton J., Roue M., Petrella S., Capton E., RA Forterre P., Aubry A., Mayer C.; RT "Mycobacterium tuberculosis DNA gyrase possesses two functional GyrA- RT boxes."; RL Biochem. J. 455:285-294(2013). CC -!- FUNCTION: A type II topoisomerase that negatively supercoils closed CC circular double-stranded (ds) DNA in an ATP-dependent manner to CC maintain chromosomes in an underwound state, while in the absence of CC ATP it relaxes supercoiled dsDNA (PubMed:15047530, PubMed:16377674, CC PubMed:16876125, PubMed:17015625, PubMed:18426901, PubMed:19060136, CC PubMed:22844097, PubMed:20805881). Also catalyzes the interconversion CC of other topological isomers of dsDNA rings, including catenanes CC (PubMed:16876125, PubMed:19060136, PubMed:22457352). Gyrase from CC M.tuberculosis has higher decatenation than supercoiling activity CC compared to E.coli; as M.tuberculosis only has 1 type II topoisomerase, CC gyrase has to fulfill the decatenation function of topoisomerase IV as CC well (PubMed:16876125, PubMed:22457352, PubMed:23869946). At comparable CC concentrations M.tuberculosis gyrase cannot introduce as many negative CC supercoils into DNA as the E.coli enzyme, and its ATPase activity is CC lower, perhaps because it does not couple DNA wrapping and ATP binding CC as well as E.coli (PubMed:22457352). {ECO:0000269|PubMed:15047530, CC ECO:0000269|PubMed:16377674, ECO:0000269|PubMed:16876125, CC ECO:0000269|PubMed:17015625, ECO:0000269|PubMed:18426901, CC ECO:0000269|PubMed:19060136, ECO:0000269|PubMed:20805881, CC ECO:0000269|PubMed:22457352, ECO:0000269|PubMed:22844097, CC ECO:0000269|PubMed:23869946}. CC -!- FUNCTION: Negative supercoiling favors strand separation, and DNA CC replication, transcription, recombination and repair, all of which CC involve strand separation. Type II topoisomerases break and join 2 DNA CC strands simultaneously in an ATP-dependent manner. 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_01897, CC ECO:0000269|PubMed:15047530, ECO:0000269|PubMed:16876125}; CC -!- COFACTOR: CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108; CC Evidence={ECO:0000269|PubMed:22844097}; CC Note=May bind up to 2 Ca(2+) per subunit, Ca(2+) does not substitute CC for supercoiling activity, but is required for relaxation, probably by CC an interaction with this subunit (PubMed:22844097). This subunit has CC altered protease sensitivity in the presence of Ca(2+), which might CC reflect regulation (PubMed:22844097). {ECO:0000269|PubMed:22844097}; CC -!- ACTIVITY REGULATION: DNA supercoiling inhibited by (fluoro)quinoline CC antibiotics such as sparfloxacin and levofloxacin, which usually act on CC GyrA (PubMed:15047530, PubMed:17015625). DNA supercoiling inhibited by CC the coumarin antibiotic novobiocin which acts on GyrB CC (PubMed:16876125). Quinolones lead to gyrase-mediated dsDNA cleavage CC while preventing reclosure (PubMed:15047530, PubMed:16876125, CC PubMed:23869946). DNA supercoiling activity inhibited by CC aminopyrazinamide and pyrrolamide derivatives, probably via effects on CC the GyrB subunit (PubMed:23268609, PubMed:24126580). DNA relaxation CC inhibited by ATP and its analogs (PubMed:16876125). DNA supercoiling, CC relaxation, decatenation and quinolone-promoted DNA cleavage are CC inhibited by MfpA (50% inhibition occurs at 2 uM), inhibition of gyrase CC activities is enhanced in a concentration-dependent manner by MfpA CC (PubMed:19060136). {ECO:0000269|PubMed:15047530, CC ECO:0000269|PubMed:16876125, ECO:0000269|PubMed:17015625, CC ECO:0000269|PubMed:19060136, ECO:0000269|PubMed:23268609, CC ECO:0000269|PubMed:23869946, ECO:0000269|PubMed:24126580}. CC -!- SUBUNIT: Heterotetramer, composed of two GyrA and two GyrB chains. In CC the heterotetramer, GyrA contains the active site tyrosine that forms a CC transient covalent intermediate with DNA, while GyrB binds cofactors CC and catalyzes ATP hydrolysis (PubMed:15047530). {ECO:0000255|HAMAP- CC Rule:MF_01897, ECO:0000269|PubMed:15047530}. CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000255|HAMAP-Rule:MF_01897}. CC -!- DOMAIN: The N-terminal domain (residues 1-502, also called GA57BK) CC forms a dimer; when reconstituted with intact GyrB or the C-terminus of CC GyrB (residues 448-675) can catalyze quinolone-mediated DNA breaks CC (PubMed:20805881). The C-terminal domain (CTD, residues 514-838) CC contains 6 tandemly repeated subdomains known as blades, each of which CC is composed of a 4-stranded antiparallel beta-sheet (PubMed:22457352, CC PubMed:23869946). The blades form a circular-shaped beta-pinwheel fold CC arranged in a spiral around a screw axis, which binds DNA CC (PubMed:22457352, PubMed:23869946). Unlike in E.coli, isolated CTD both CC binds and wraps DNA and is able to introduce writhe into DNA, but the CC holoenzyme in M.tuberculosis is missing the GyrA acidic tail found in CC E.coli and thus does not couple DNA wrapping and ATP binding as well as CC E.coli (PubMed:22457352). There are 2 GyrA-boxes in the CTD; mutations CC in GyrA-box (residues 537-543, the canonical box) affect supercoiling CC but not decatenation, those in GyrA-box-1 (residues 743-749, conserved CC in some Actinobacteria) affect both, suggesting there is a novel DNA- CC binding pathway in M.tuberculosis compared to E.coli (PubMed:23869946). CC {ECO:0000269|PubMed:20805881, ECO:0000269|PubMed:22457352, CC ECO:0000269|PubMed:23869946}. CC -!- MISCELLANEOUS: When the enzyme transiently cleaves DNA a CC phosphotyrosine bond is formed between GyrA and DNA (PubMed:15047530). CC In the presence of quinolones this intermediate can be trapped and is CC used as an indicator of drug toxicity (PubMed:16377674, CC PubMed:23869946). DNA gyrase is intrinsically more resistant to CC fluoroquinolone drugs than in E.coli, mutating it to resemble E.coli CC increases its susceptibility to fluoroquinolones (most quinolone- CC resistant mutations are in this subunit) (PubMed:18426901). CC {ECO:0000269|PubMed:18426901, ECO:0000305|PubMed:15047530, CC ECO:0000305|PubMed:16377674, ECO:0000305|PubMed:23869946}. CC -!- MISCELLANEOUS: Gyrase from M.tuberculosis is usually assayed in the CC presence of potassium glutamate (KGlu); KGlu stimulates supercoiling CC but inhibits DNA relaxation activity, and has concentration-dependent CC effects on GyrA-box mutants (PubMed:16876125, PubMed:23869946). CC {ECO:0000269|PubMed:16876125, ECO:0000269|PubMed:23869946}. CC -!- SIMILARITY: Belongs to the type II topoisomerase GyrA/ParC subunit CC family. {ECO:0000255|HAMAP-Rule:MF_01897}. 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; L27512; AAA83017.1; -; Genomic_DNA. DR EMBL; JX303241; AFR90330.1; -; Genomic_DNA. DR EMBL; AL123456; CCP42728.1; -; Genomic_DNA. DR EMBL; L11919; AAC36878.1; -; Unassigned_DNA. DR EMBL; X72872; CAA51386.1; -; Genomic_DNA. DR PIR; D70698; D70698. DR RefSeq; NP_214520.1; NC_000962.3. DR RefSeq; WP_003917265.1; NZ_NVQJ01000005.1. DR PDB; 3IFZ; X-ray; 2.70 A; A/B=1-501. DR PDB; 3ILW; X-ray; 1.60 A; A/B=34-500. DR PDB; 3UC1; X-ray; 1.65 A; A=514-838. DR PDB; 4G3N; X-ray; 1.40 A; A=512-838. DR PDB; 5BS8; X-ray; 2.40 A; A/C=2-500. DR PDB; 5BTA; X-ray; 2.55 A; A/C=2-500. DR PDB; 5BTC; X-ray; 2.55 A; A/C=2-500. DR PDB; 5BTD; X-ray; 2.50 A; A/C=2-500. DR PDB; 5BTF; X-ray; 2.61 A; A/C=2-500. DR PDB; 5BTG; X-ray; 2.50 A; A/C=2-500. DR PDB; 5BTI; X-ray; 2.50 A; A/C=2-500. DR PDB; 5BTL; X-ray; 2.50 A; A/C=2-500. DR PDB; 5BTN; X-ray; 2.50 A; A/C=2-500. DR PDB; 6GAU; X-ray; 3.30 A; A/B=2-501. DR PDB; 6GAV; X-ray; 2.60 A; A/B=2-501. DR PDB; 7UGW; X-ray; 3.00 A; A/C=2-501. DR PDBsum; 3IFZ; -. DR PDBsum; 3ILW; -. DR PDBsum; 3UC1; -. DR PDBsum; 4G3N; -. DR PDBsum; 5BS8; -. DR PDBsum; 5BTA; -. DR PDBsum; 5BTC; -. DR PDBsum; 5BTD; -. DR PDBsum; 5BTF; -. DR PDBsum; 5BTG; -. DR PDBsum; 5BTI; -. DR PDBsum; 5BTL; -. DR PDBsum; 5BTN; -. DR PDBsum; 6GAU; -. DR PDBsum; 6GAV; -. DR PDBsum; 7UGW; -. DR AlphaFoldDB; P9WG47; -. DR SMR; P9WG47; -. DR STRING; 83332.Rv0006; -. DR BindingDB; P9WG47; -. DR ChEMBL; CHEMBL4165; -. DR DrugCentral; P9WG47; -. DR iPTMnet; P9WG47; -. DR PaxDb; 83332-Rv0006; -. DR DNASU; 887105; -. DR GeneID; 887105; -. DR KEGG; mtu:Rv0006; -. DR TubercuList; Rv0006; -. DR eggNOG; COG0188; Bacteria. DR InParanoid; P9WG47; -. DR OrthoDB; 9806486at2; -. DR PhylomeDB; P9WG47; -. DR BRENDA; 5.6.2.2; 3445. DR PRO; PR:P9WG47; -. DR Proteomes; UP000001584; Chromosome. DR GO; GO:0005694; C:chromosome; IEA:InterPro. DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central. DR GO; GO:0009330; C:DNA topoisomerase type II (double strand cut, ATP-hydrolyzing) complex; IBA:GO_Central. DR GO; GO:0009274; C:peptidoglycan-based cell wall; HDA:MTBBASE. DR GO; GO:0005886; C:plasma membrane; HDA:MTBBASE. DR GO; GO:0005524; F:ATP binding; IDA:MTBBASE. DR GO; GO:0016887; F:ATP hydrolysis activity; IDA:MTBBASE. DR GO; GO:0003677; F:DNA binding; IBA:GO_Central. DR GO; GO:0034335; F:DNA negative supercoiling activity; IDA:UniProtKB. DR GO; GO:0003918; F:DNA topoisomerase type II (double strand cut, ATP-hydrolyzing) activity; IDA:MTBBASE. DR GO; GO:0000287; F:magnesium ion binding; IDA:MTBBASE. DR GO; GO:0006265; P:DNA topological change; IDA:MTBBASE. DR GO; GO:0006261; P:DNA-templated DNA replication; IEA:UniProtKB-UniRule. DR GO; GO:0046677; P:response to antibiotic; IEA:UniProtKB-KW. DR CDD; cd00187; TOP4c; 1. DR Gene3D; 3.30.1360.40; -; 1. DR Gene3D; 2.120.10.90; DNA gyrase/topoisomerase IV, subunit A, C-terminal; 1. DR Gene3D; 3.90.199.10; Topoisomerase II, domain 5; 1. DR Gene3D; 1.10.268.10; Topoisomerase, domain 3; 1. DR HAMAP; MF_01897; GyrA; 1. DR InterPro; IPR005743; GyrA. 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 NCBIfam; TIGR01063; gyrA; 1. DR PANTHER; PTHR43493:SF5; DNA GYRASE SUBUNIT A, CHLOROPLASTIC/MITOCHONDRIAL; 1. DR PANTHER; PTHR43493; DNA GYRASE/TOPOISOMERASE SUBUNIT A; 1. DR Pfam; PF03989; DNA_gyraseA_C; 6. DR Pfam; PF00521; DNA_topoisoIV; 1. DR SMART; SM00434; TOP4c; 1. DR SUPFAM; SSF101904; GyrA/ParC C-terminal domain-like; 1. DR SUPFAM; SSF56719; Type II DNA topoisomerase; 1. DR PROSITE; PS00018; EF_HAND_1; 1. DR PROSITE; PS52040; TOPO_IIA; 1. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Antibiotic resistance; ATP-binding; Calcium; KW Cytoplasm; DNA-binding; Isomerase; Metal-binding; Nucleotide-binding; KW Reference proteome; Topoisomerase. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0007744|PubMed:21969609" FT CHAIN 2..838 FT /note="DNA gyrase subunit A" FT /id="PRO_0000145243" FT DOMAIN 41..510 FT /note="Topo IIA-type catalytic" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01384" FT DOMAIN 504..516 FT /note="EF-hand" FT /evidence="ECO:0000305|PubMed:22844097" FT REGION 514..838 FT /note="C-terminal domain CTD" FT /evidence="ECO:0000303|PubMed:22457352, FT ECO:0000303|PubMed:23869946" FT MOTIF 537..543 FT /note="GyrA-box" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01897, FT ECO:0000303|PubMed:23869946" FT MOTIF 743..749 FT /note="GyrA-box-1" FT /evidence="ECO:0000303|PubMed:23869946" FT ACT_SITE 129 FT /note="O-(5'-phospho-DNA)-tyrosine intermediate" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01897" FT BINDING 504 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10142" FT BINDING 506 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10142" FT BINDING 508 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10142" FT BINDING 515 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10142" FT MOD_RES 2 FT /note="N-acetylthreonine" FT /evidence="ECO:0007744|PubMed:21969609" FT VARIANT 90 FT /note="A -> V (confers ciprofloxacin resistance, in FT clinical isolate)" FT /evidence="ECO:0000269|PubMed:8031045" FT VARIANT 91 FT /note="S -> P (confers ciprofloxacin resistance, in FT clinical isolate)" FT /evidence="ECO:0000269|PubMed:8031045" FT VARIANT 94 FT /note="D -> A (confers ciprofloxacin resistance, in FT clinical isolate)" FT /evidence="ECO:0000269|PubMed:8031045" FT VARIANT 94 FT /note="D -> G (confers ciprofloxacin resistance, in FT clinical isolate)" FT /evidence="ECO:0000269|PubMed:8031045" FT VARIANT 94 FT /note="D -> H (confers ciprofloxacin resistance, in FT clinical isolate)" FT /evidence="ECO:0000269|PubMed:8031045" FT VARIANT 94 FT /note="D -> N (confers ciprofloxacin resistance, in FT clinical isolate)" FT /evidence="ECO:0000269|PubMed:8031045" FT VARIANT 94 FT /note="D -> Y (confers ciprofloxacin resistance, in FT clinical isolate)" FT /evidence="ECO:0000269|PubMed:8031045" FT MUTAGEN 80 FT /note="T->A: Slight resistance to fluoroquinolones. FT Hypersusceptibile, 2- to 14-fold higher sensitivity to FT fluoroquinolones, 2- to 8-fold more efficient in FT fluoroquinolone-induced DNA cleavage; when associated with FT G-90." FT /evidence="ECO:0000269|PubMed:16377674" FT MUTAGEN 88 FT /note="G->A: Confers fluoroquinolone resistance, IC(50) is FT 2- to 26-fold higher than wild-type." FT /evidence="ECO:0000269|PubMed:17015625" FT MUTAGEN 88 FT /note="G->C: Confers fluoroquinolone resistance, IC(50) is FT 3- to 43-fold higher than wild-type, in strains H37Ra and FT H37Rv." FT /evidence="ECO:0000269|PubMed:17015625, FT ECO:0000269|PubMed:8031045" FT MUTAGEN 90..94 FT /note="ASIYD->VSIYG: 80-fold increased resistance to FT fluoroquinolones, 32- to 64-fold reduction in FT fluoroquinolone-induced DNA cleavage." FT /evidence="ECO:0000269|PubMed:16377674" FT MUTAGEN 90 FT /note="A->G: 4- to 16-fold more efficient in FT fluoroquinolone-induced DNA cleavage alone. FT Hypersusceptibile, 2- to 14-fold higher sensitivity to FT fluoroquinolones, 2- to 8-fold more efficient in FT fluoroquinolone-induced DNA cleavage; when associated with FT A-80." FT /evidence="ECO:0000269|PubMed:16377674" FT MUTAGEN 90 FT /note="A->S: Increased susceptibility to fluoroquinolones FT (makes sequence more like E.coli), supercoiling, FT relaxation, decatenation activities still inhibited by FT MfpA." FT /evidence="ECO:0000269|PubMed:18426901, FT ECO:0000269|PubMed:19060136" FT MUTAGEN 90 FT /note="A->V: 17-fold increased resistance to FT fluoroquinolones, 4- to 8-fold reduction in FT fluoroquinolone-induced DNA cleavage." FT /evidence="ECO:0000269|PubMed:16377674" FT MUTAGEN 94 FT /note="D->G,H: 25- 45-fold increased resistance to FT fluoroquinolones, 4- to 8-fold reduction in FT fluoroquinolone-induced DNA cleavage. Supercoiling, FT relaxation, decatenation activities no longer inhibited by FT MfpA." FT /evidence="ECO:0000269|PubMed:16377674, FT ECO:0000269|PubMed:19060136" FT MUTAGEN 94 FT /note="D->H: Confers ofloxacin resistance." FT /evidence="ECO:0000269|PubMed:8035042" FT MUTAGEN 504..514 FT /note="DVSDEDLIARE->AVSDAALIARA: Significant reduction in FT DNA wrapping and supercoiling activity, no change in FT decatanation or relaxation activities." FT /evidence="ECO:0000269|PubMed:22844097" FT MUTAGEN 508..509 FT /note="ED->AA: Slight reduction in supercoiling activity." FT /evidence="ECO:0000269|PubMed:22844097" FT MUTAGEN 538 FT /note="K->R: Wild-type decatenase activity (changes residue FT to match E.coli)." FT /evidence="ECO:0000269|PubMed:23869946" FT MUTAGEN 540..543 FT /note="GGKG->AAKA: No supercoiling activity, almost wild- FT type decatenation activity, wild-type fluoroquinolone- FT induced DNA cleavage." FT /evidence="ECO:0000269|PubMed:23869946" FT MUTAGEN 540 FT /note="G->A: No change in supercoiling activity, wild-type FT decatenation or fluoroquinolone-induced DNA cleavage." FT /evidence="ECO:0000269|PubMed:23869946" FT MUTAGEN 541 FT /note="G->A: Reduced supercoiling activity, wild-type FT decatenation and fluoroquinolone-induced DNA cleavage." FT /evidence="ECO:0000269|PubMed:23869946" FT MUTAGEN 543 FT /note="G->A: Reduced supercoiling activity, wild-type FT decatenation and fluoroquinolone-induced DNA cleavage." FT /evidence="ECO:0000269|PubMed:23869946" FT MUTAGEN 543 FT /note="G->K: No supercoiling activity, wild-type FT decatenation and fluoroquinolone-induced DNA cleavage." FT /evidence="ECO:0000269|PubMed:23869946" FT MUTAGEN 544..545 FT /note="VQ->KS: Wild-type decatenase activity (changes FT residues to match E.coli)." FT /evidence="ECO:0000269|PubMed:23869946" FT MUTAGEN 746..749 FT /note="GGKG->AAKA: No supercoiling or decatenation FT activity, decreased fluoroquinolone-induced DNA cleavage." FT /evidence="ECO:0000269|PubMed:23869946" FT MUTAGEN 746 FT /note="G->A: Wild-type supercoiling, decatenation and FT fluoroquinolone-induced DNA cleavage." FT /evidence="ECO:0000269|PubMed:23869946" FT MUTAGEN 747 FT /note="G->A: Wild-type supercoiling, decatenation and FT fluoroquinolone-induced DNA cleavage." FT /evidence="ECO:0000269|PubMed:23869946" FT MUTAGEN 749 FT /note="G->A: No supercoiling or decatenation activity, FT decreased fluoroquinolone-induced DNA cleavage." FT /evidence="ECO:0000269|PubMed:23869946" FT CONFLICT 83 FT /note="N -> K (in Ref. 4; AAC36878)" FT /evidence="ECO:0000305" FT CONFLICT 712 FT /note="L -> V (in Ref. 1; AAA83017)" FT /evidence="ECO:0000305" FT STRAND 16..19 FT /evidence="ECO:0007829|PDB:5BS8" FT HELIX 20..37 FT /evidence="ECO:0007829|PDB:6GAU" FT TURN 38..40 FT /evidence="ECO:0007829|PDB:3ILW" FT TURN 44..46 FT /evidence="ECO:0007829|PDB:3ILW" FT HELIX 50..62 FT /evidence="ECO:0007829|PDB:3ILW" FT STRAND 66..68 FT /evidence="ECO:0007829|PDB:6GAU" FT HELIX 73..83 FT /evidence="ECO:0007829|PDB:3ILW" FT HELIX 91..100 FT /evidence="ECO:0007829|PDB:3ILW" FT TURN 102..104 FT /evidence="ECO:0007829|PDB:3ILW" FT STRAND 109..114 FT /evidence="ECO:0007829|PDB:3ILW" FT STRAND 119..121 FT /evidence="ECO:0007829|PDB:3ILW" FT HELIX 127..129 FT /evidence="ECO:0007829|PDB:5BS8" FT STRAND 131..134 FT /evidence="ECO:0007829|PDB:3ILW" FT HELIX 136..142 FT /evidence="ECO:0007829|PDB:3ILW" FT HELIX 145..147 FT /evidence="ECO:0007829|PDB:3ILW" FT STRAND 152..154 FT /evidence="ECO:0007829|PDB:3ILW" FT STRAND 158..165 FT /evidence="ECO:0007829|PDB:3ILW" FT HELIX 172..176 FT /evidence="ECO:0007829|PDB:3ILW" FT STRAND 178..181 FT /evidence="ECO:0007829|PDB:5BS8" FT STRAND 186..189 FT /evidence="ECO:0007829|PDB:5BS8" FT HELIX 194..206 FT /evidence="ECO:0007829|PDB:3ILW" FT TURN 207..209 FT /evidence="ECO:0007829|PDB:3ILW" FT HELIX 212..222 FT /evidence="ECO:0007829|PDB:3ILW" FT STRAND 233..235 FT /evidence="ECO:0007829|PDB:3ILW" FT HELIX 238..246 FT /evidence="ECO:0007829|PDB:3ILW" FT STRAND 247..254 FT /evidence="ECO:0007829|PDB:3ILW" FT STRAND 256..261 FT /evidence="ECO:0007829|PDB:3ILW" FT STRAND 263..265 FT /evidence="ECO:0007829|PDB:5BS8" FT STRAND 267..273 FT /evidence="ECO:0007829|PDB:3ILW" FT HELIX 280..292 FT /evidence="ECO:0007829|PDB:3ILW" FT STRAND 299..304 FT /evidence="ECO:0007829|PDB:3ILW" FT TURN 308..310 FT /evidence="ECO:0007829|PDB:3ILW" FT STRAND 314..318 FT /evidence="ECO:0007829|PDB:3ILW" FT STRAND 320..322 FT /evidence="ECO:0007829|PDB:6GAU" FT HELIX 324..334 FT /evidence="ECO:0007829|PDB:3ILW" FT STRAND 338..344 FT /evidence="ECO:0007829|PDB:3ILW" FT STRAND 346..349 FT /evidence="ECO:0007829|PDB:3ILW" FT STRAND 352..355 FT /evidence="ECO:0007829|PDB:3ILW" FT HELIX 358..399 FT /evidence="ECO:0007829|PDB:3ILW" FT HELIX 401..410 FT /evidence="ECO:0007829|PDB:3ILW" FT STRAND 411..413 FT /evidence="ECO:0007829|PDB:6GAU" FT HELIX 414..425 FT /evidence="ECO:0007829|PDB:3ILW" FT HELIX 429..436 FT /evidence="ECO:0007829|PDB:3ILW" FT HELIX 440..443 FT /evidence="ECO:0007829|PDB:3ILW" FT HELIX 445..470 FT /evidence="ECO:0007829|PDB:3ILW" FT HELIX 472..490 FT /evidence="ECO:0007829|PDB:3ILW" FT STRAND 496..499 FT /evidence="ECO:0007829|PDB:3ILW" FT STRAND 515..521 FT /evidence="ECO:0007829|PDB:4G3N" FT STRAND 524..530 FT /evidence="ECO:0007829|PDB:4G3N" FT HELIX 531..534 FT /evidence="ECO:0007829|PDB:4G3N" FT HELIX 551..553 FT /evidence="ECO:0007829|PDB:4G3N" FT STRAND 555..562 FT /evidence="ECO:0007829|PDB:4G3N" FT STRAND 565..571 FT /evidence="ECO:0007829|PDB:4G3N" FT STRAND 574..580 FT /evidence="ECO:0007829|PDB:4G3N" FT HELIX 581..583 FT /evidence="ECO:0007829|PDB:4G3N" FT STRAND 589..591 FT /evidence="ECO:0007829|PDB:3UC1" FT HELIX 596..599 FT /evidence="ECO:0007829|PDB:4G3N" FT STRAND 608..616 FT /evidence="ECO:0007829|PDB:4G3N" FT STRAND 619..627 FT /evidence="ECO:0007829|PDB:4G3N" FT STRAND 630..636 FT /evidence="ECO:0007829|PDB:4G3N" FT HELIX 637..640 FT /evidence="ECO:0007829|PDB:4G3N" FT STRAND 645..650 FT /evidence="ECO:0007829|PDB:4G3N" FT STRAND 659..665 FT /evidence="ECO:0007829|PDB:4G3N" FT STRAND 670..675 FT /evidence="ECO:0007829|PDB:4G3N" FT STRAND 678..684 FT /evidence="ECO:0007829|PDB:4G3N" FT TURN 687..689 FT /evidence="ECO:0007829|PDB:4G3N" FT STRAND 695..697 FT /evidence="ECO:0007829|PDB:4G3N" FT STRAND 700..702 FT /evidence="ECO:0007829|PDB:4G3N" FT STRAND 711..716 FT /evidence="ECO:0007829|PDB:4G3N" FT STRAND 722..727 FT /evidence="ECO:0007829|PDB:4G3N" FT STRAND 730..736 FT /evidence="ECO:0007829|PDB:4G3N" FT HELIX 737..739 FT /evidence="ECO:0007829|PDB:4G3N" FT STRAND 750..753 FT /evidence="ECO:0007829|PDB:4G3N" FT TURN 757..759 FT /evidence="ECO:0007829|PDB:4G3N" FT STRAND 762..768 FT /evidence="ECO:0007829|PDB:4G3N" FT STRAND 773..781 FT /evidence="ECO:0007829|PDB:4G3N" FT STRAND 783..787 FT /evidence="ECO:0007829|PDB:4G3N" FT HELIX 788..790 FT /evidence="ECO:0007829|PDB:4G3N" FT STRAND 812..818 FT /evidence="ECO:0007829|PDB:4G3N" SQ SEQUENCE 838 AA; 92274 MW; 84DAFE13D74D76D7 CRC64; MTDTTLPPDD SLDRIEPVDI EQEMQRSYID YAMSVIVGRA LPEVRDGLKP VHRRVLYAMF DSGFRPDRSH AKSARSVAET MGNYHPHGDA SIYDSLVRMA QPWSLRYPLV DGQGNFGSPG NDPPAAMRYT EARLTPLAME MLREIDEETV DFIPNYDGRV QEPTVLPSRF PNLLANGSGG IAVGMATNIP PHNLRELADA VFWALENHDA DEEETLAAVM GRVKGPDFPT AGLIVGSQGT ADAYKTGRGS IRMRGVVEVE EDSRGRTSLV ITELPYQVNH DNFITSIAEQ VRDGKLAGIS NIEDQSSDRV GLRIVIEIKR DAVAKVVINN LYKHTQLQTS FGANMLAIVD GVPRTLRLDQ LIRYYVDHQL DVIVRRTTYR LRKANERAHI LRGLVKALDA LDEVIALIRA SETVDIARAG LIELLDIDEI QAQAILDMQL RRLAALERQR IIDDLAKIEA EIADLEDILA KPERQRGIVR DELAEIVDRH GDDRRTRIIA ADGDVSDEDL IAREDVVVTI TETGYAKRTK TDLYRSQKRG GKGVQGAGLK QDDIVAHFFV CSTHDLILFF TTQGRVYRAK AYDLPEASRT ARGQHVANLL AFQPEERIAQ VIQIRGYTDA PYLVLATRNG LVKKSKLTDF DSNRSGGIVA VNLRDNDELV GAVLCSAGDD LLLVSANGQS IRFSATDEAL RPMGRATSGV QGMRFNIDDR LLSLNVVREG TYLLVATSGG YAKRTAIEEY PVQGRGGKGV LTVMYDRRRG RLVGALIVDD DSELYAVTSG GGVIRTAARQ VRKAGRQTKG VRLMNLGEGD TLLAIARNAE ESGDDNAVDA NGADQTGN //