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 11-MAY-2016, entry version 22. DE RecName: Full=DNA gyrase subunit A {ECO:0000255|HAMAP-Rule:MF_01897}; DE EC=5.99.1.3 {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; Actinobacteria; Corynebacteriales; Mycobacteriaceae; OC Mycobacterium; Mycobacterium tuberculosis complex. OX NCBI_TaxID=83332; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS VAL-90; PRO-91; ALA-94; RP GLY-94; HIS-94; ASN-94 AND TYR-94, MUTAGENESIS OF GLY-88, AND RP ANTIBIOTIC 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 RT and 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 RT in 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., RA Harris D.E., Gordon S.V., Eiglmeier K., Gas S., Barry C.E. III, RA Tekaia F., Badcock K., Basham D., Brown D., Chillingworth T., RA Connor R., Davies R.M., Devlin K., Feltwell T., Gentles S., Hamlin N., RA Holroyd S., Hornsby T., Jagels K., Krogh A., McLean J., Moule S., RA Murphy L.D., Oliver S., Osborne J., Quail M.A., Rajandream M.A., RA Rogers J., Rutter S., Seeger K., Skelton S., Squares S., Squares R., RA Sulston J.E., Taylor K., Whitehead S., Barrell B.G.; RT "Deciphering the biology of Mycobacterium tuberculosis from the RT complete 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 RT gene segments from mycobacteria."; RL Gene 136:287-290(1993). RN [5] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 89-124, MUTAGENESIS OF ASP-94, RP AND 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, ENZYME 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 RT and 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 RT of mutant enzymes."; RL Antimicrob. Agents Chemother. 50:104-112(2006). RN [8] RP FUNCTION, CATALYTIC ACTIVITY, AND ENZYME 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 RT type II topoisomerase: the enzyme from Mycobacterium tuberculosis."; RL Biochem. Biophys. Res. Commun. 348:158-165(2006). RN [9] RP FUNCTION, ENZYME 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., RA Camuset J., Bouvet E., Cambau E., Aubry A.; RT "Functional analysis of DNA gyrase mutant enzymes carrying mutations RT at position 88 in the A subunit found in clinical strains of RT Mycobacterium 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 RT of GyrB refines the contribution of Mycobacterium tuberculosis DNA RT gyrase to intrinsic resistance to quinolones."; RL Antimicrob. Agents Chemother. 52:2909-2914(2008). RN [11] RP FUNCTION, ENZYME 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 RT effects on DNA gyrase catalytic reactions and on the ternary gyrase- RT DNA-quinolone 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 RP 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., RA Yadav A.K., Shrivastava P., Marimuthu A., Anand S., Sundaram H., RA Kingsbury R., Harsha H.C., Nair B., Prasad T.S., Chauhan D.S., RA Katoch K., Katoch V.M., Kumar P., Chaerkady R., Ramachandran S., RA Dash D., Pandey A.; RT "Proteogenomic analysis of Mycobacterium tuberculosis by high RT resolution 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 ENZYME 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., RA Sharma S., Ramya V.K., Narayan C.B., Balganesh T.S., RA 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 ENZYME 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., RA Ghosh A., Awasthy D., Shanbhag G., Sheikh G., McMiken H., Puttur J., RA Reddy J., Werngren J., Read J., Kumar M., R M., Chinnapattu M., RA Madhavapeddi P., Manjrekar P., Basu R., Gaonkar S., Sharma S., RA Hoffner S., Humnabadkar V., 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 RT of 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., RA Aubry A., 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, RP AND 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 RT orthologs: II. The shape of the GyrA subunit C-terminal domain (CTD) RT is not a sole 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 RP AND 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 CC closed circular double-stranded (ds) DNA in an ATP-dependent CC manner to maintain chromosomes in an underwound state, while in CC the absence of ATP it relaxes supercoiled dsDNA (PubMed:15047530, CC PubMed:16377674, PubMed:16876125, PubMed:17015625, CC PubMed:18426901, PubMed:19060136, PubMed:22844097, CC PubMed:20805881). Also catalyzes the interconversion of other CC 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 CC topoisomerase, gyrase has to fulfill the decatenation function of CC topoisomerase IV as well (PubMed:16876125, PubMed:22457352, CC PubMed:23869946). At comparable concentrations M.tuberculosis CC gyrase cannot introduce as many negative supercoils into DNA as CC the E.coli enzyme, and its ATPase activity is lower, perhaps CC because it does not couple DNA wrapping and ATP binding as well as CC 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 CC DNA strands simultaneously in an ATP-dependent manner. CC -!- CATALYTIC ACTIVITY: ATP-dependent breakage, passage and rejoining CC of double-stranded DNA. {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 CC substitute for supercoiling activity, but is required for CC relaxation, probably by an interaction with this subunit CC (PubMed:22844097). This subunit has altered protease sensitivity CC in the presence of Ca(2+), which might reflect regulation CC (PubMed:22844097). {ECO:0000269|PubMed:22844097}; CC -!- ENZYME REGULATION: DNA supercoiling inhibited by (fluoro)quinoline CC antibiotics such as sparfloxacin and levofloxacin, which usually CC act on GyrA (PubMed:15047530, PubMed:17015625). DNA supercoiling CC inhibited by the coumarin antibiotic novobiocin which acts on GyrB CC (PubMed:16876125). Quinolones lead to gyrase-mediated dsDNA CC cleavage while preventing reclosure (PubMed:15047530, CC PubMed:16876125, PubMed:23869946). DNA supercoiling activity CC inhibited by aminopyrazinamide and pyrrolamide derivatives, CC probably via effects on the GyrB subunit (PubMed:23268609, CC PubMed:24126580). DNA relaxation inhibited by ATP and its analogs CC (PubMed:16876125). DNA supercoiling, relaxation, decatenation and CC quinolone-promoted DNA cleavage are inhibited by MfpA (50% CC inhibition occurs at 2 uM), inhibition of gyrase activites is CC 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. CC In the heterotetramer, GyrA contains the active site tyrosine that CC forms a transient covalent intermediate with DNA, while GyrB binds CC cofactors and catalyzes ATP hydrolysis (PubMed:15047530). CC {ECO:0000255|HAMAP-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- CC terminus of GyrB (residues 448-675) can catalyze quinolone- CC mediated DNA breaks (PubMed:20805881). The C-terminal domain (CTD, CC residues 514-838) contains 6 tandemly repeated subdomains known as CC blades, each of which is composed of a 4-stranded antiparallel CC beta-sheet (PubMed:22457352, PubMed:23869946). The blades form a CC circular-shaped beta-pinwheel fold arranged in a spiral around a CC screw axis, which binds DNA (PubMed:22457352, PubMed:23869946). CC Unlike in E.coli, isolated CTD both binds and wraps DNA and is CC able to introduce writhe into DNA, but the holoenzyme in CC M.tuberculosis is missing the GyrA acidic tail found in E.coli and CC 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; CC mutations in GyrA-box (residues 537-543, the canonical box) affect CC supercoiling but not decatenation, those in GyrA-box-1 (residues CC 743-749, conserved in some Actinobacteria) affect both, suggesting CC there is a novel DNA-binding pathway in M.tuberculosis compared to CC E.coli (PubMed:23869946). {ECO:0000269|PubMed:20805881, CC ECO:0000269|PubMed:22457352, ECO:0000269|PubMed:23869946}. CC -!- MISCELLANEOUS: When the enzyme transiently cleaves DNA a CC phosphotyrosine bond is formed between GyrA and DNA CC (PubMed:15047530). In the presence of quinolones this intermediate CC can be trapped and is used as an indicator of drug toxicity CC (PubMed:16377674, PubMed:23869946). DNA gyrase is intrinsically CC more resistant to fluoroquinolone drugs than in E.coli, mutating CC it to resemble E.coli increases its susceptibility to CC fluoroquinolones (most quinolone-resistant mutations are in this CC subunit) (PubMed:18426901). {ECO:0000269|PubMed:18426901, CC ECO:0000305|PubMed:15047530, ECO:0000305|PubMed:16377674, CC ECO:0000305|PubMed:23869946}. CC -!- MISCELLANEOUS: Gyrase from M.tuberculosis is usually assayed in CC the presence of potassium glutamate (KGlu); KGlu stimulates CC supercoiling but inhibits DNA relaxation activity, and has CC concentration-dependent effects on GyrA-box mutants CC (PubMed:16876125, PubMed:23869946). {ECO:0000269|PubMed:16876125, CC ECO:0000269|PubMed:23869946}. CC -!- SIMILARITY: Belongs to the type II topoisomerase GyrA/ParC subunit CC family. {ECO:0000255|HAMAP-Rule:MF_01897}. CC -!- SIMILARITY: Contains 1 EF-hand domain. CC {ECO:0000305|PubMed:22844097}. 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_KK339370.1. 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 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 ProteinModelPortal; P9WG47; -. DR SMR; P9WG47; 9-501, 512-820. DR STRING; 83332.Rv0006; -. DR ChEMBL; CHEMBL4165; -. DR PaxDb; P9WG47; -. DR EnsemblBacteria; CCP42728; CCP42728; Rv0006. DR GeneID; 887105; -. DR KEGG; mtu:Rv0006; -. DR TubercuList; Rv0006; -. DR eggNOG; ENOG4105C24; Bacteria. DR eggNOG; COG0188; LUCA. DR KO; K02469; -. DR PhylomeDB; P9WG47; -. DR PRO; PR:P9WG47; -. DR Proteomes; UP000001584; Chromosome. DR GO; GO:0005618; C:cell wall; IDA:MTBBASE. DR GO; GO:0005694; C:chromosome; IEA:InterPro. DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell. DR GO; GO:0009295; C:nucleoid; IBA:GO_Central. DR GO; GO:0005886; C:plasma membrane; IDA:MTBBASE. DR GO; GO:0005524; F:ATP binding; IDA:MTBBASE. DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-HAMAP. DR GO; GO:0034335; F:DNA supercoiling activity; IDA:UniProtKB. DR GO; GO:0003918; F:DNA topoisomerase type II (ATP-hydrolyzing) activity; IDA:MTBBASE. DR GO; GO:0000287; F:magnesium ion binding; IDA:MTBBASE. DR GO; GO:0007059; P:chromosome segregation; IBA:GO_Central. DR GO; GO:0006265; P:DNA topological change; IDA:MTBBASE. DR GO; GO:0006261; P:DNA-dependent DNA replication; IEA:UniProtKB-HAMAP. DR GO; GO:0046677; P:response to antibiotic; IEA:UniProtKB-KW. DR Gene3D; 3.30.1360.40; -; 1. DR Gene3D; 3.90.199.10; -; 2. DR HAMAP; MF_01897; GyrA; 1. DR InterPro; IPR024946; Arg_repress_C-like. DR InterPro; IPR005743; GyrA. DR InterPro; IPR006691; GyrA/parC_pinwhl. DR InterPro; IPR013760; Topo_IIA-like_dom. DR InterPro; IPR002205; Topo_IIA_A/C. DR InterPro; IPR013758; Topo_IIA_A/C_ab. DR Pfam; PF03989; DNA_gyraseA_C; 6. DR Pfam; PF00521; DNA_topoisoIV; 1. DR SMART; SM00434; TOP4c; 1. DR SUPFAM; SSF56719; SSF56719; 1. DR TIGRFAMs; TIGR01063; gyrA; 1. DR PROSITE; PS00018; EF_HAND_1; 1. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Antibiotic resistance; ATP-binding; KW Calcium; Complete proteome; Cytoplasm; DNA-binding; Isomerase; KW Nucleotide-binding; Reference proteome; Topoisomerase. FT INIT_MET 1 1 Removed. {ECO:0000244|PubMed:21969609}. FT CHAIN 2 838 DNA gyrase subunit A. FT /FTId=PRO_0000145243. FT DOMAIN 504 516 EF-hand. {ECO:0000305|PubMed:22844097}. FT CA_BIND 504 516 {ECO:0000305|PubMed:22844097}. FT REGION 514 838 C-terminal domain CTD. FT {ECO:0000303|PubMed:22457352, FT ECO:0000303|PubMed:23869946}. FT MOTIF 537 543 GyrA-box. {ECO:0000255|HAMAP- FT Rule:MF_01897, FT ECO:0000303|PubMed:23869946}. FT MOTIF 743 749 GyrA-box-1. FT {ECO:0000303|PubMed:23869946}. FT ACT_SITE 129 129 O-(5'-phospho-DNA)-tyrosine intermediate. FT {ECO:0000255|HAMAP-Rule:MF_01897}. FT MOD_RES 2 2 N-acetylthreonine. FT {ECO:0000244|PubMed:21969609}. FT VARIANT 90 90 A -> V (confers ciprofloxacin resistance, FT in clinical isolate). FT {ECO:0000269|PubMed:8031045}. FT VARIANT 91 91 S -> P (confers ciprofloxacin resistance, FT in clinical isolate). FT {ECO:0000269|PubMed:8031045}. FT VARIANT 94 94 D -> A (confers ciprofloxacin resistance, FT in clinical isolate). FT {ECO:0000269|PubMed:8031045}. FT VARIANT 94 94 D -> G (confers ciprofloxacin resistance, FT in clinical isolate). FT {ECO:0000269|PubMed:8031045}. FT VARIANT 94 94 D -> H (confers ciprofloxacin resistance, FT in clinical isolate). FT {ECO:0000269|PubMed:8031045}. FT VARIANT 94 94 D -> N (confers ciprofloxacin resistance, FT in clinical isolate). FT {ECO:0000269|PubMed:8031045}. FT VARIANT 94 94 D -> Y (confers ciprofloxacin resistance, FT in clinical isolate). FT {ECO:0000269|PubMed:8031045}. FT MUTAGEN 80 80 T->A: Slight resistance to FT fluoroquinolones. Hypersusceptibile, 2-to FT 14-fold higher sensitivity to FT fluoroquinolones, 2- to 8-fold more FT efficient in fluoroquinolone-induced DNA FT cleavage; when associated with G-90. FT {ECO:0000269|PubMed:16377674}. FT MUTAGEN 88 88 G->A: Confers fluoroquinolone resistance, FT IC(50) is 2- to 26-fold higher than wild- FT type. {ECO:0000269|PubMed:17015625}. FT MUTAGEN 88 88 G->C: Confers fluoroquinolone resistance, FT IC(50) is 3- to 43-fold higher than wild- FT type, in strains H37Ra and H37Rv. FT {ECO:0000269|PubMed:17015625, FT ECO:0000269|PubMed:8031045}. FT MUTAGEN 90 94 ASIYD->VSIYG: 80-fold increased FT resistance to fluoroquinolones, 32- to FT 64-fold reduction in fluoroquinolone- FT induced DNA cleavage. FT {ECO:0000269|PubMed:16377674}. FT MUTAGEN 90 90 A->G: 4- to 16-fold more efficient in FT fluoroquinolone-induced DNA cleavage FT alone. Hypersusceptibile, 2- to 14-fold FT higher sensitivity to fluoroquinolones, FT 2- to 8-fold more efficient in FT fluoroquinolone-induced DNA cleavage; FT when associated with A-80. FT {ECO:0000269|PubMed:16377674}. FT MUTAGEN 90 90 A->S: Increased susceptibility to FT fluoroquinolones (makes sequence more FT like E.coli), supercoiling, relaxation, FT decatenation activities still inhibited FT by MfpA. {ECO:0000269|PubMed:18426901, FT ECO:0000269|PubMed:19060136}. FT MUTAGEN 90 90 A->V: 17-fold increased resistance to FT fluoroquinolones, 4- to 8-fold reduction FT in fluoroquinolone-induced DNA cleavage. FT {ECO:0000269|PubMed:16377674}. FT MUTAGEN 94 94 D->G,H: 25- 45-fold increased resistance FT to fluoroquinolones, 4- to 8-fold FT reduction in fluoroquinolone-induced DNA FT cleavage. Supercoiling, relaxation, FT decatenation activities no longer FT inhibited by MfpA. FT {ECO:0000269|PubMed:16377674, FT ECO:0000269|PubMed:19060136}. FT MUTAGEN 94 94 D->H: Confers ofloxacin resistance. FT {ECO:0000269|PubMed:8035042}. FT MUTAGEN 504 514 DVSDEDLIARE->AVSDAALIARA: Significant FT reduction in DNA wrapping and FT supercoiling activity, no change in FT decatanation or relaxation activities. FT {ECO:0000269|PubMed:22844097}. FT MUTAGEN 508 509 ED->AA: Slight reduction in supercoiling FT activity. {ECO:0000269|PubMed:22844097}. FT MUTAGEN 538 538 K->R: Wild-type decatenase activity FT (changes residue to match E.coli). FT {ECO:0000269|PubMed:23869946}. FT MUTAGEN 540 543 GGKG->AAKA: No supercoiling activity, FT almost wild-type decatenation activity, FT wild-type fluoroquinolone-induced DNA FT cleavage. {ECO:0000269|PubMed:23869946}. FT MUTAGEN 540 540 G->A: No change in supercoiling activity, FT wild-type decatenation or FT fluoroquinolone-induced DNA cleavage. FT {ECO:0000269|PubMed:23869946}. FT MUTAGEN 541 541 G->A: Reduced supercoiling activity, FT wild-type decatenation and FT fluoroquinolone-induced DNA cleavage. FT {ECO:0000269|PubMed:23869946}. FT MUTAGEN 543 543 G->A: Reduced supercoiling activity, FT wild-type decatenation and FT fluoroquinolone-induced DNA cleavage. FT {ECO:0000269|PubMed:23869946}. FT MUTAGEN 543 543 G->K: No supercoiling activity, wild-type FT decatenation and fluoroquinolone-induced FT DNA cleavage. FT {ECO:0000269|PubMed:23869946}. FT MUTAGEN 544 545 VQ->KS: Wild-type decatenase activity FT (changes residues to match E.coli). FT {ECO:0000269|PubMed:23869946}. FT MUTAGEN 746 749 GGKG->AAKA: No supercoiling or FT decatenation activity, decreased FT fluoroquinolone-induced DNA cleavage. FT {ECO:0000269|PubMed:23869946}. FT MUTAGEN 746 746 G->A: Wild-type supercoiling, FT decatenation and fluoroquinolone-induced FT DNA cleavage. FT {ECO:0000269|PubMed:23869946}. FT MUTAGEN 747 747 G->A: Wild-type supercoiling, FT decatenation and fluoroquinolone-induced FT DNA cleavage. FT {ECO:0000269|PubMed:23869946}. FT MUTAGEN 749 749 G->A: No supercoiling or decatenation FT activity, decreased fluoroquinolone- FT induced DNA cleavage. FT {ECO:0000269|PubMed:23869946}. FT CONFLICT 83 83 N -> K (in Ref. 4; AAC36878). FT {ECO:0000305}. FT CONFLICT 712 712 L -> V (in Ref. 1; AAA83017). FT {ECO:0000305}. FT STRAND 16 19 {ECO:0000244|PDB:5BS8}. FT TURN 38 40 {ECO:0000244|PDB:3ILW}. FT TURN 44 46 {ECO:0000244|PDB:3ILW}. FT HELIX 50 62 {ECO:0000244|PDB:3ILW}. FT HELIX 73 83 {ECO:0000244|PDB:3ILW}. FT HELIX 91 100 {ECO:0000244|PDB:3ILW}. FT TURN 102 104 {ECO:0000244|PDB:3ILW}. FT STRAND 109 114 {ECO:0000244|PDB:3ILW}. FT STRAND 119 121 {ECO:0000244|PDB:3ILW}. FT HELIX 127 129 {ECO:0000244|PDB:5BS8}. FT STRAND 131 134 {ECO:0000244|PDB:3ILW}. FT HELIX 136 142 {ECO:0000244|PDB:3ILW}. FT HELIX 145 147 {ECO:0000244|PDB:3ILW}. FT STRAND 152 154 {ECO:0000244|PDB:3ILW}. FT STRAND 158 165 {ECO:0000244|PDB:3ILW}. FT HELIX 172 176 {ECO:0000244|PDB:3ILW}. FT STRAND 178 181 {ECO:0000244|PDB:5BS8}. FT STRAND 186 189 {ECO:0000244|PDB:5BS8}. FT HELIX 194 206 {ECO:0000244|PDB:3ILW}. FT TURN 207 209 {ECO:0000244|PDB:3ILW}. FT HELIX 212 222 {ECO:0000244|PDB:3ILW}. FT STRAND 233 235 {ECO:0000244|PDB:3ILW}. FT HELIX 238 246 {ECO:0000244|PDB:3ILW}. FT STRAND 247 254 {ECO:0000244|PDB:3ILW}. FT STRAND 256 261 {ECO:0000244|PDB:3ILW}. FT STRAND 263 265 {ECO:0000244|PDB:5BS8}. FT STRAND 267 273 {ECO:0000244|PDB:3ILW}. FT HELIX 280 292 {ECO:0000244|PDB:3ILW}. FT STRAND 299 304 {ECO:0000244|PDB:3ILW}. FT TURN 308 310 {ECO:0000244|PDB:3ILW}. FT STRAND 314 318 {ECO:0000244|PDB:3ILW}. FT HELIX 324 334 {ECO:0000244|PDB:3ILW}. FT STRAND 338 344 {ECO:0000244|PDB:3ILW}. FT STRAND 346 349 {ECO:0000244|PDB:3ILW}. FT STRAND 352 355 {ECO:0000244|PDB:3ILW}. FT HELIX 358 399 {ECO:0000244|PDB:3ILW}. FT HELIX 401 410 {ECO:0000244|PDB:3ILW}. FT HELIX 414 425 {ECO:0000244|PDB:3ILW}. FT HELIX 429 436 {ECO:0000244|PDB:3ILW}. FT HELIX 440 443 {ECO:0000244|PDB:3ILW}. FT HELIX 445 470 {ECO:0000244|PDB:3ILW}. FT HELIX 472 490 {ECO:0000244|PDB:3ILW}. FT STRAND 496 499 {ECO:0000244|PDB:3ILW}. FT STRAND 515 521 {ECO:0000244|PDB:4G3N}. FT STRAND 524 530 {ECO:0000244|PDB:4G3N}. FT HELIX 531 534 {ECO:0000244|PDB:4G3N}. FT HELIX 551 553 {ECO:0000244|PDB:4G3N}. FT STRAND 555 562 {ECO:0000244|PDB:4G3N}. FT STRAND 565 571 {ECO:0000244|PDB:4G3N}. FT STRAND 574 580 {ECO:0000244|PDB:4G3N}. FT HELIX 581 583 {ECO:0000244|PDB:4G3N}. FT STRAND 589 591 {ECO:0000244|PDB:3UC1}. FT HELIX 596 599 {ECO:0000244|PDB:4G3N}. FT STRAND 608 616 {ECO:0000244|PDB:4G3N}. FT STRAND 619 627 {ECO:0000244|PDB:4G3N}. FT STRAND 630 636 {ECO:0000244|PDB:4G3N}. FT HELIX 637 640 {ECO:0000244|PDB:4G3N}. FT STRAND 645 650 {ECO:0000244|PDB:4G3N}. FT STRAND 659 665 {ECO:0000244|PDB:4G3N}. FT STRAND 670 675 {ECO:0000244|PDB:4G3N}. FT STRAND 678 684 {ECO:0000244|PDB:4G3N}. FT TURN 687 689 {ECO:0000244|PDB:4G3N}. FT STRAND 695 697 {ECO:0000244|PDB:4G3N}. FT STRAND 700 702 {ECO:0000244|PDB:4G3N}. FT STRAND 711 716 {ECO:0000244|PDB:4G3N}. FT STRAND 722 727 {ECO:0000244|PDB:4G3N}. FT STRAND 730 736 {ECO:0000244|PDB:4G3N}. FT HELIX 737 739 {ECO:0000244|PDB:4G3N}. FT STRAND 750 753 {ECO:0000244|PDB:4G3N}. FT TURN 757 759 {ECO:0000244|PDB:4G3N}. FT STRAND 762 768 {ECO:0000244|PDB:4G3N}. FT STRAND 773 781 {ECO:0000244|PDB:4G3N}. FT STRAND 783 787 {ECO:0000244|PDB:4G3N}. FT HELIX 788 790 {ECO:0000244|PDB:4G3N}. FT STRAND 812 818 {ECO:0000244|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 //