GYRA_MYCTU
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 03-AUG-2022, entry version 57.
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; 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; 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.m111.011627;
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).
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}.
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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 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 AlphaFoldDB; P9WG47; -.
DR SMR; P9WG47; -.
DR STRING; 83332.Rv0006; -.
DR BindingDB; P9WG47; -.
DR ChEMBL; CHEMBL4165; -.
DR DrugCentral; P9WG47; -.
DR iPTMnet; P9WG47; -.
DR PaxDb; P9WG47; -.
DR DNASU; 887105; -.
DR GeneID; 887105; -.
DR KEGG; mtu:Rv0006; -.
DR TubercuList; Rv0006; -.
DR eggNOG; COG0188; Bacteria.
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; 1.10.268.10; -; 1.
DR Gene3D; 2.120.10.90; -; 1.
DR Gene3D; 3.90.199.10; -; 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 Pfam; PF03989; DNA_gyraseA_C; 6.
DR Pfam; PF00521; DNA_topoisoIV; 1.
DR SMART; SM00434; TOP4c; 1.
DR SUPFAM; SSF101904; SSF101904; 1.
DR SUPFAM; SSF56719; SSF56719; 1.
DR PROSITE; PS00018; EF_HAND_1; 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 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
