ID GYRA_ECOLI Reviewed; 875 AA. AC P0AES4; P09097; DT 20-DEC-2005, integrated into UniProtKB/Swiss-Prot. DT 20-DEC-2005, sequence version 1. DT 02-SEP-2026, entry version 173. 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:12051842, ECO:0000269|PubMed:18642932, ECO:0000269|PubMed:186775, ECO:0000269|PubMed:19965760, ECO:0000269|PubMed:9278055}; GN Name=gyrA {ECO:0000255|HAMAP-Rule:MF_01897}; GN Synonyms=hisW, nalA {ECO:0000303|PubMed:337300}, parD; GN OrderedLocusNames=b2231, JW2225; OS Escherichia coli (strain K12). OC Bacteria; Pseudomonadati; Pseudomonadota; Gammaproteobacteria; OC Enterobacterales; Enterobacteriaceae; Escherichia. OX NCBI_TaxID=83333; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=2828631; DOI=10.1016/0022-2836(87)90479-7; RA Swanberg S.L., Wang J.C.; RT "Cloning and sequencing of the Escherichia coli gyrA gene coding for the A RT subunit of DNA gyrase."; RL J. Mol. Biol. 197:729-736(1987). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RC STRAIN=K12 / KL16; RX PubMed=2830458; DOI=10.1007/bf00338386; RA Yoshida H., Kojima T., Yamagishi J., Nakamura S.; RT "Quinolone-resistant mutations of the gyrA gene of Escherichia coli."; RL Mol. Gen. Genet. 211:1-7(1988). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT NAL-113 ASN-87, AND VARIANT OV6 RP MET-MET-ILE-798 INS. RC STRAIN=OV6; RX PubMed=2834621; DOI=10.1111/j.1365-2958.1987.tb01932.x; RA Hussain K., Elliott E.J., Salmond G.P.C.; RT "The parD- mutant of Escherichia coli also carries a gyrAam mutation. The RT complete sequence of gyrA."; RL Mol. Microbiol. 1:259-273(1987). RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS QUINOLONE-RESISTANT GLU-678 RP AND SER-828. RC STRAIN=227; RX PubMed=2548439; DOI=10.1128/aac.33.6.886; RA Cullen M.E., Wyke A.W., Kuroda R., Fisher L.M.; RT "Cloning and characterization of a DNA gyrase A gene from Escherichia coli RT that confers clinical resistance to 4-quinolones."; RL Antimicrob. Agents Chemother. 33:886-894(1989). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=K12 / W3110 / ATCC 27325 / DSM 5911; RX PubMed=9205837; DOI=10.1093/dnares/4.2.91; RA Yamamoto Y., Aiba H., Baba T., Hayashi K., Inada T., Isono K., Itoh T., RA Kimura S., Kitagawa M., Makino K., Miki T., Mitsuhashi N., Mizobuchi K., RA Mori H., Nakade S., Nakamura Y., Nashimoto H., Oshima T., Oyama S., RA Saito N., Sampei G., Satoh Y., Sivasundaram S., Tagami H., Takahashi H., RA Takeda J., Takemoto K., Uehara K., Wada C., Yamagata S., Horiuchi T.; RT "Construction of a contiguous 874-kb sequence of the Escherichia coli-K12 RT genome corresponding to 50.0-68.8 min on the linkage map and analysis of RT its sequence features."; RL DNA Res. 4:91-113(1997). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=K12 / MG1655 / ATCC 47076; RX PubMed=9278503; DOI=10.1126/science.277.5331.1453; RA Blattner F.R., Plunkett G. III, Bloch C.A., Perna N.T., Burland V., RA Riley M., Collado-Vides J., Glasner J.D., Rode C.K., Mayhew G.F., RA Gregor J., Davis N.W., Kirkpatrick H.A., Goeden M.A., Rose D.J., Mau B., RA Shao Y.; RT "The complete genome sequence of Escherichia coli K-12."; RL Science 277:1453-1462(1997). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=K12 / W3110 / ATCC 27325 / DSM 5911; RX PubMed=16738553; DOI=10.1038/msb4100049; RA Hayashi K., Morooka N., Yamamoto Y., Fujita K., Isono K., Choi S., RA Ohtsubo E., Baba T., Wanner B.L., Mori H., Horiuchi T.; RT "Highly accurate genome sequences of Escherichia coli K-12 strains MG1655 RT and W3110."; RL Mol. Syst. Biol. 2:E1-E5(2006). RN [8] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-88, AND PARTIAL PROTEIN SEQUENCE. RX PubMed=3029031; DOI=10.1128/jb.169.3.1272-1278.1987; RA Menzel R., Gellert M.; RT "Fusions of the Escherichia coli gyrA and gyrB control regions to the RT galactokinase gene are inducible by coumermycin treatment."; RL J. Bacteriol. 169:1272-1278(1987). RN [9] RP PROTEIN SEQUENCE OF 17-24; 61-66 AND 123-126, FUNCTION, ACTIVE SITE, RP REACTION MECHANISM, AND DNA-BINDING. RX PubMed=3031051; DOI=10.1016/s0021-9258(18)61193-7; RA Horowitz D.S., Wang J.C.; RT "Mapping the active site tyrosine of Escherichia coli DNA gyrase."; RL J. Biol. Chem. 262:5339-5344(1987). RN [10] RP FUNCTION IN GENERATING NEGATIVELY SUPERCOILED DNA, CATALYTIC ACTIVITY, AND RP ATP-DEPENDENCE. RX PubMed=186775; DOI=10.1073/pnas.73.11.3872; RA Gellert M., Mizuuchi K., O'Dea M.H., Nash H.A.; RT "DNA gyrase: an enzyme that introduces superhelical turns into DNA."; RL Proc. Natl. Acad. Sci. U.S.A. 73:3872-3876(1976). RN [11] RP FUNCTION IN RELAXING SUPERCOILED DNA, AND ACTIVITY REGULATION. RX PubMed=337300; DOI=10.1073/pnas.74.11.4772; RA Gellert M., Mizuuchi K., O'Dea M.H., Itoh T., Tomizawa J.I.; RT "Nalidixic acid resistance: a second genetic character involved in DNA RT gyrase activity."; RL Proc. Natl. Acad. Sci. U.S.A. 74:4772-4776(1977). RN [12] RP VARIANTS QUINOLONE-RESISTANT SER-67; CYS-81; LEU-83; TRP-83; PRO-84; ASN-87 RP AND HIS-106. RC STRAIN=K12 / KL16; RX PubMed=2168148; DOI=10.1128/aac.34.6.1271; RA Yoshida H., Bogaki M., Nakamura M., Nakamura S.; RT "Quinolone resistance-determining region in the DNA gyrase gyrA gene of RT Escherichia coli."; RL Antimicrob. Agents Chemother. 34:1271-1272(1990). RN [13] RP VARIANTS QUINOLONE-RESISTANT LEU-83; TRP-83 AND VAL-87. RX PubMed=1850972; DOI=10.1128/aac.35.2.387; RA Oram M., Fisher L.M.; RT "4-quinolone resistance mutations in the DNA gyrase of Escherichia coli RT clinical isolates identified by using the polymerase chain reaction."; RL Antimicrob. Agents Chemother. 35:387-389(1991). RN [14] RP MUTAGENESIS OF SER-83 AND GLN-106. RC STRAIN=K12; RX PubMed=1850970; DOI=10.1128/aac.35.2.335; RA Hallett P., Maxwell A.; RT "Novel quinolone resistance mutations of the Escherichia coli DNA gyrase A RT protein: enzymatic analysis of the mutant proteins."; RL Antimicrob. Agents Chemother. 35:335-340(1991). RN [15] RP INHIBITION BY TOXIN PROTEIN CCDB, AND MUTAGENESIS OF ARG-462. RC STRAIN=K12; RX PubMed=1324324; DOI=10.1016/0022-2836(92)90629-x; RA Bernard P., Couturier M.; RT "Cell killing by the F plasmid CcdB protein involves poisoning of DNA- RT topoisomerase II complexes."; RL J. Mol. Biol. 226:735-745(1992). RN [16] RP MUTAGENESIS OF ARG-462. RX PubMed=8254658; DOI=10.1006/jmbi.1993.1609; RA Bernard P., Kezdy K.E., Van Melderen L., Steyaert J., Wyns L., Pato M.L., RA Higgins P.N., Couturier M.; RT "The F plasmid CcdB protein induces efficient ATP-dependent DNA cleavage by RT gyrase."; RL J. Mol. Biol. 234:534-541(1993). RN [17] RP FUNCTION, AND ACTIVITY REGULATION. RX PubMed=7811004; DOI=10.1128/aac.38.9.1966; RA Nakada N., Gmuender H., Hirata T., Arisawa M.; RT "Mechanism of inhibition of DNA gyrase by cyclothialidine, a novel DNA RT gyrase inhibitor."; RL Antimicrob. Agents Chemother. 38:1966-1973(1994). RN [18] RP INHIBITION BY TOXIN PROTEIN CCDB, REJUVENATION BY CCDA, AND SUBUNIT. RX PubMed=8604132; DOI=10.1006/jmbi.1996.0102; RA Maki S., Takiguchi S., Horiuchi T., Sekimizu K., Miki T.; RT "Partner switching mechanisms in inactivation and rejuvenation of RT Escherichia coli DNA gyrase by F plasmid proteins LetD (CcdB) and LetA RT (CcdA)."; RL J. Mol. Biol. 256:473-482(1996). RN [19] RP FUNCTION, AND DOMAIN. RX PubMed=8962066; DOI=10.1073/pnas.93.25.14416; RA Kampranis S.C., Maxwell A.; RT "Conversion of DNA gyrase into a conventional type II topoisomerase."; RL Proc. Natl. Acad. Sci. U.S.A. 93:14416-14421(1996). RN [20] RP FUNCTION, ACTIVITY REGULATION, SUBUNIT, AND DNA-BINDING. RC STRAIN=K12 / N2879; RX PubMed=9148951; DOI=10.1074/jbc.272.20.13302; RA Funatsuki K., Tanaka R., Inagaki S., Konno H., Katoh K., Nakamura H.; RT "acrB mutation located at carboxyl-terminal region of gyrase B subunit RT reduces DNA binding of DNA gyrase."; RL J. Biol. Chem. 272:13302-13308(1997). RN [21] RP IDENTIFICATION BY 2D-GEL. RX PubMed=9298644; DOI=10.1002/elps.1150180805; RA VanBogelen R.A., Abshire K.Z., Moldover B., Olson E.R., Neidhardt F.C.; RT "Escherichia coli proteome analysis using the gene-protein database."; RL Electrophoresis 18:1243-1251(1997). RN [22] RP FUNCTION. RX PubMed=9334322; DOI=10.1101/gad.11.19.2580; RA Zechiedrich E.L., Khodursky A.B., Cozzarelli N.R.; RT "Topoisomerase IV, not gyrase, decatenates products of site-specific RT recombination in Escherichia coli."; RL Genes Dev. 11:2580-2592(1997). RN [23] RP IDENTIFICATION AND DISCUSSION OF GYRA-BOX, AND DOMAIN. RX PubMed=9426128; DOI=10.1046/j.1365-2958.1997.6242005.x; RA Ward D.V., Newton A.; RT "Requirement of topoisomerase IV parC and parE genes for cell cycle RT progression and developmental regulation in Caulobacter crescentus."; RL Mol. Microbiol. 26:897-910(1997). RN [24] RP FUNCTION, CATALYTIC ACTIVITY, SUBUNIT, AND MUTAGENESIS OF ARG-32; ARG-47; RP HIS-78 AND HIS-80. RX PubMed=12051842; DOI=10.1016/s0022-2836(02)00048-7; RA Hockings S.C., Maxwell A.; RT "Identification of four GyrA residues involved in the DNA breakage-reunion RT reaction of DNA gyrase."; RL J. Mol. Biol. 318:351-359(2002). RN [25] RP FUNCTION, AND MUTAGENESIS OF 560-GLN--GLY-566. RX PubMed=16332690; DOI=10.1074/jbc.m511160200; RA Kramlinger V.M., Hiasa H.; RT "The 'GyrA-box' is required for the ability of DNA gyrase to wrap DNA and RT catalyze the supercoiling reaction."; RL J. Biol. Chem. 281:3738-3742(2006). RN [26] RP FUNCTION. RC STRAIN=K12 / W3110 / ATCC 27325 / DSM 5911; RX PubMed=17400739; DOI=10.1128/jb.00083-07; RA Champion K., Higgins N.P.; RT "Growth rate toxicity phenotypes and homeostatic supercoil control RT differentiate Escherichia coli from Salmonella enterica serovar RT Typhimurium."; RL J. Bacteriol. 189:5839-5849(2007). RN [27] RP FUNCTION, CATALYTIC ACTIVITY, AND SUBUNIT. RX PubMed=18642932; DOI=10.1021/bi800480j; RA Sissi C., Chemello A., Vazquez E., Mitchenall L.A., Maxwell A., Palumbo M.; RT "DNA gyrase requires DNA for effective two-site coordination of divalent RT metal ions: further insight into the mechanism of enzyme action."; RL Biochemistry 47:8538-8545(2008). RN [28] RP FUNCTION, AND ACTIVITY REGULATION. 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 [29] RP FUNCTION, AND ACTIVITY REGULATION. RX PubMed=20356737; DOI=10.1016/j.bmcl.2010.03.052; RA Ronkin S.M., Badia M., Bellon S., Grillot A.L., Gross C.H., Grossman T.H., RA Mani N., Parsons J.D., Stamos D., Trudeau M., Wei Y., Charifson P.S.; RT "Discovery of pyrazolthiazoles as novel and potent inhibitors of bacterial RT gyrase."; RL Bioorg. Med. Chem. Lett. 20:2828-2831(2010). RN [30] RP FUNCTION, DOMAIN, DNA-BINDING, AND MUTAGENESIS OF 842-PRO--ALA-856 AND RP 854-SER--GLU-875. RX PubMed=22457353; DOI=10.1074/jbc.m112.345678; RA Tretter E.M., Berger J.M.; RT "Mechanisms for defining supercoiling set point of DNA gyrase orthologs: I. RT A nonconserved acidic C-terminal tail modulates Escherichia coli gyrase RT activity."; RL J. Biol. Chem. 287:18636-18644(2012). RN [31] RP FUNCTION, DNA-BINDING, AND MUTAGENESIS OF 842-PRO--ALA-856. 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 [32] RP FUNCTION, AND ACTIVITY REGULATION. RX PubMed=23294697; DOI=10.1016/j.bmcl.2012.11.073; RA Trzoss M., Bensen D.C., Li X., Chen Z., Lam T., Zhang J., Creighton C.J., RA Cunningham M.L., Kwan B., Stidham M., Nelson K., Brown-Driver V., RA Castellano A., Shaw K.J., Lightstone F.C., Wong S.E., Nguyen T.B., Finn J., RA Tari L.W.; RT "Pyrrolopyrimidine inhibitors of DNA gyrase B (GyrB) and topoisomerase IV RT (ParE), Part II: development of inhibitors with broad spectrum, Gram- RT negative antibacterial activity."; RL Bioorg. Med. Chem. Lett. 23:1537-1543(2013). RN [33] RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 30-522, AND CATALYTIC ACTIVITY. RX PubMed=9278055; DOI=10.1038/42294; RA Morais Cabral J.H., Jackson A.P., Smith C.V., Shikotra N., Maxwell A., RA Liddington R.C.; RT "Crystal structure of the breakage-reunion domain of DNA gyrase."; RL Nature 388:903-906(1997). RN [34] RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 363-494 IN COMPLEX WITH CCBD, AND RP SUBUNIT. RX PubMed=15854646; DOI=10.1016/j.jmb.2005.03.049; RA Dao-Thi M.H., Van Melderen L., De Genst E., Afif H., Buts L., Wyns L., RA Loris R.; RT "Molecular basis of gyrase poisoning by the addiction toxin CcdB."; RL J. Mol. Biol. 348:1091-1102(2005). RN [35] RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 535-841, AND DOMAIN. RC STRAIN=K12; RX PubMed=15897198; DOI=10.1074/jbc.m502838200; RA Ruthenburg A.J., Graybosch D.M., Huetsch J.C., Verdine G.L.; RT "A superhelical spiral in the Escherichia coli DNA gyrase A C-terminal RT domain imparts unidirectional supercoiling bias."; RL J. Biol. Chem. 280:26177-26184(2005). RN [36] RP X-RAY CRYSTALLOGRAPHY (2.62 ANGSTROMS) OF 1-525 IN COMPLEX WITH ANTIBIOTIC, RP FUNCTION, CATALYTIC ACTIVITY, AND SUBUNIT. RX PubMed=19965760; DOI=10.1126/science.1179123; RA Edwards M.J., Flatman R.H., Mitchenall L.A., Stevenson C.E., Le T.B., RA Clarke T.A., McKay A.R., Fiedler H.P., Buttner M.J., Lawson D.M., RA Maxwell A.; RT "A crystal structure of the bifunctional antibiotic simocyclinone D8, bound RT to DNA gyrase."; RL Science 326:1415-1418(2009). 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 (PubMed:12051842, CC PubMed:18642932, PubMed:186775, PubMed:19060136, PubMed:19965760, CC PubMed:20356737, PubMed:22457353, PubMed:23294697, PubMed:3031051, CC PubMed:7811004, PubMed:9148951). This makes better substrates for CC topoisomerase IV (ParC and ParE) which is the main enzyme that unlinks CC newly replicated chromosomes in E.coli (PubMed:9334322). Gyrase CC catalyzes the interconversion of other topological isomers of dsDNA CC rings, including catenanes (PubMed:22457352). Relaxes negatively CC supercoiled DNA in an ATP-independent manner (PubMed:337300). E.coli CC gyrase has higher supercoiling activity than many other bacterial CC gyrases; at comparable concentrations E.coli gyrase introduces more CC supercoils faster than M.tuberculosis gyrase, while M.tuberculosis CC gyrase has higher decatenation than supercoiling activity compared to CC E.coli (PubMed:22457352). E.coli makes 15% more negative supercoils in CC pBR322 plasmid DNA than S.typhimurium; the S.typhimurium GyrB subunit CC is toxic in E.coli, while the E.coli copy can be expressed in CC S.typhimurium even though the 2 subunits have 777/804 residues CC identical (PubMed:17400739). The enzymatic differences between E.coli CC gyrase and topoisomerase IV are largely due to the GyrA C-terminal CC domain (approximately residues 524-841) and specifically the GyrA-box CC (PubMed:16332690, PubMed:8962066). {ECO:0000269|PubMed:12051842, CC ECO:0000269|PubMed:16332690, ECO:0000269|PubMed:17400739, CC ECO:0000269|PubMed:18642932, ECO:0000269|PubMed:186775, CC ECO:0000269|PubMed:19060136, ECO:0000269|PubMed:19965760, CC ECO:0000269|PubMed:20356737, ECO:0000269|PubMed:22457352, CC ECO:0000269|PubMed:22457353, ECO:0000269|PubMed:23294697, CC ECO:0000269|PubMed:3031051, ECO:0000269|PubMed:337300, CC ECO:0000269|PubMed:7811004, ECO:0000269|PubMed:8962066, CC ECO:0000269|PubMed:9148951, ECO:0000269|PubMed:9334322}. 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:12051842, ECO:0000269|PubMed:18642932, CC ECO:0000269|PubMed:186775, ECO:0000269|PubMed:19965760, CC ECO:0000269|PubMed:9278055}; CC -!- ACTIVITY REGULATION: Gyrase is the target of many classes of CC inhibitors, including coumarins, cyclothialidines, pyrrolopyrimidines, CC pyrazolthiazoles and (fluoro)quinolones. Quinolones bind GyrA when the CC enzyme is complexed with DNA and trap the enzyme in a covalent reaction CC intermediate with DNA (PubMed:12051842, PubMed:3031051). Coumarins bind CC to GyrB and are competitive inhibitors of its ATPase activity CC (PubMed:7811004). Cyclothialidines also bind GyrB and are ATPase CC competitive inhibitors; they seem to act differently from coumarins CC (PubMed:7811004). Pyrrolopyrimidines inhibit both GyrB and its paralog CC in topoisomerase IV (parE) (PubMed:23294697). Pyrazolthiazoles also CC inhibit the ATPase activity of GyrB (PubMed:20356737). DNA supercoiling CC and relaxation are both inhibited by oxolinic acid (PubMed:337300). CC Acriflavine inhibits supercoiling activity and DNA-stimulated ATPase CC activity (PubMed:9148951). DNA supercoiling activity is protected from CC fluoroquinolone inhibition by QnrB4; QnrB4 has no effect on CC supercoiling activity alone (PubMed:19060136). CC {ECO:0000269|PubMed:19060136, ECO:0000269|PubMed:20356737, CC ECO:0000269|PubMed:23294697, ECO:0000269|PubMed:337300, CC ECO:0000269|PubMed:7811004, ECO:0000269|PubMed:9148951}. CC -!- SUBUNIT: Heterotetramer, composed of two GyrA and two GyrB chains CC (PubMed:12051842, PubMed:9148951). In the heterotetramer, GyrA contains CC the active site tyrosine that forms a transient covalent intermediate CC with the DNA, while GyrB binds cofactors and catalyzes ATP hydrolysis CC (PubMed:12051842, PubMed:18642932, PubMed:19965760, PubMed:9148951). CC Can form a 2:2 complex with toxin CcdB in which GyrA is inactive; CC rejuvenation of GyrA(2)CcdB(2) is effected by CcdA (PubMed:1324324, CC PubMed:15854646, PubMed:8254658, PubMed:8604132). CC {ECO:0000269|PubMed:12051842, ECO:0000269|PubMed:1324324, CC ECO:0000269|PubMed:15854646, ECO:0000269|PubMed:18642932, CC ECO:0000269|PubMed:19965760, ECO:0000269|PubMed:8254658, CC ECO:0000269|PubMed:8604132, ECO:0000269|PubMed:9148951}. CC -!- INTERACTION: CC P0AES4; P62554: ccdB; NbExp=3; IntAct=EBI-547129, EBI-25647730; CC P0AES4; P0AES4: gyrA; NbExp=6; IntAct=EBI-547129, EBI-547129; CC P0AES4; P0AES6: gyrB; NbExp=7; IntAct=EBI-547129, EBI-541911; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000255|HAMAP-Rule:MF_01897}. CC -!- DOMAIN: An N-terminal fragment (residues 1-523) can be reconstituted CC with GyrB, but the complex no longer has negative supercoiling or ATP- CC independent DNA relaxation activities, although it is capable of DNA CC cleavage; ATP-dependent relaxation is inhibited by novobiocin and non- CC hydrolyzable ATP analogs (PubMed:8962066). The fragment has ATP- CC dependent DNA relaxation and 30-fold improved decatenation activities, CC unlike holoenzyme it preferentially binds supercoiled DNA CC (PubMed:8962066). This N-terminal fragment becomes a topoisomerase IV- CC like enzyme; it poorly complements a temperature-sensitive parC CC mutation (parC is the topoisomerase IV paralog of gyrA) CC (PubMed:8962066). {ECO:0000269|PubMed:8962066}. CC -!- DOMAIN: The C-terminal domain (CTD, approximately residues 535-841) CC contains 6 tandemly repeated subdomains known as blades, each of which CC is composed of a 4-stranded antiparallel beta-sheet (PubMed:15897198). CC The blades form a circular-shaped beta-pinwheel fold arranged in a CC spiral around a screw axis, to which DNA probably binds, inducing CC strong positive superhelicity (about 0.8 links/protein) CC (PubMed:15897198). The non-conserved, C-terminal acidic tail (residues CC 842-875) regulates wrapping and DNA-binding by the CTD; deletions CC within the tail show it is autoinhibitory for DNA wrapping and binding, CC and couples ATP hydrolysis to DNA strand passage (PubMed:22457353). The CC GyrA-box is a 7 amino acid motif found in the first blade of the CTD CC which is discriminative for gyrase versus topoisomerase IV activity CC (PubMed:9426128). The GyrA-box is required for wrapping of DNA around CC gyrase, and thus is essential for the DNA supercoiling activity but not CC DNA relaxation or decatenation activities of gyrase (PubMed:16332690). CC {ECO:0000269|PubMed:15897198, ECO:0000269|PubMed:16332690, CC ECO:0000269|PubMed:22457353, ECO:0000305|PubMed:9426128}. CC -!- MISCELLANEOUS: When the enzyme transiently cleaves DNA a CC phosphotyrosine bond is formed between GyrA and DNA (PubMed:3031051). CC In the presence of quinolones this intermediate can be trapped and is CC used as an indicator of drug toxicity (PubMed:12051842). The enzyme-DNA CC intermediate is also the target of a number of topoisomerase poisons, CC including toxin CcdB (PubMed:1324324, PubMed:8254658). CC {ECO:0000269|PubMed:1324324, ECO:0000269|PubMed:3031051, CC ECO:0000269|PubMed:8254658, ECO:0000305|PubMed:12051842}. CC -!- MISCELLANEOUS: Few gyrases are as efficient as E.coli at forming CC negative supercoils (PubMed:17400739, PubMed:22457352). Not all CC organisms have 2 type II topoisomerases; in organisms with a single CC type II topoisomerase this enzyme also has to decatenate newly CC replicated chromosomes. {ECO:0000255|HAMAP-Rule:MF_01897, CC ECO:0000269|PubMed:17400739, ECO:0000269|PubMed:22457352}. 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; X06373; CAA29676.1; -; Genomic_DNA. DR EMBL; X06744; CAA29919.1; -; Genomic_DNA. DR EMBL; M15631; AAA23948.1; -; Genomic_DNA. DR EMBL; U00096; AAC75291.1; -; Genomic_DNA. DR EMBL; AP009048; BAA16048.1; -; Genomic_DNA. DR EMBL; Y00544; CAA68611.1; -; Genomic_DNA. DR PIR; S02340; ITECAP. DR RefSeq; NP_416734.1; NC_000913.3. DR RefSeq; WP_001281242.1; NZ_CP009789.1. DR PDB; 1AB4; X-ray; 2.80 A; A=30-522. DR PDB; 1X75; X-ray; 2.80 A; A/B=363-494. DR PDB; 1ZI0; X-ray; 2.60 A; A/B=535-841. DR PDB; 2Y3P; X-ray; 2.62 A; A/B=2-523. DR PDB; 3NUH; X-ray; 3.10 A; A=1-525. DR PDB; 4ELY; X-ray; 1.93 A; A/B=363-497. DR PDB; 6RKS; EM; 4.00 A; A/C=1-875. DR PDB; 6RKU; EM; 4.00 A; A/C=1-875. DR PDB; 6RKV; EM; 4.60 A; A/C=1-875. DR PDB; 6RKW; EM; 6.60 A; A/C=1-875. DR PDB; 7Z9C; EM; 3.06 A; A/C=2-875. DR PDB; 7Z9G; EM; 3.25 A; A/C=2-875. DR PDB; 7Z9K; EM; 3.25 A; A/C=2-875. DR PDB; 7Z9M; EM; 3.30 A; A/C=2-875. DR PDB; 8QDX; EM; 3.00 A; A/C=1-875. DR PDB; 8QQI; EM; 2.90 A; A/C=2-524. DR PDB; 8QQS; EM; 2.90 A; A/C=1-875. DR PDB; 8QQU; EM; 2.90 A; C=1-875. DR PDB; 9GBV; EM; 2.32 A; A/C=2-875. DR PDB; 9GGQ; EM; 2.60 A; A/C=2-875. DR AlphaFoldDB; P0AES4; -. DR EMDB; EMD-14570; -. DR EMDB; EMD-14572; -. DR EMDB; EMD-14573; -. DR EMDB; EMD-14574; -. DR EMDB; EMD-18342; -. DR EMDB; EMD-18603; -. DR EMDB; EMD-18605; -. DR EMDB; EMD-4909; -. DR EMDB; EMD-4910; -. DR EMDB; EMD-4912; -. DR EMDB; EMD-4913; -. DR EMDB; EMD-51218; -. DR EMDB; EMD-51222; -. DR EMDB; EMD-51339; -. DR MDposit; P0AES4; -. DR SMR; P0AES4; -. DR BioGRID; 4262132; 308. DR BioGRID; 850960; 1. DR ComplexPortal; CPX-2177; GyrA-GyrB DNA Gyrase complex. DR ComplexPortal; CPX-5906; CcdB-poisoned gyrase complex. DR DIP; DIP-36179N; -. DR FunCoup; P0AES4; 567. DR IntAct; P0AES4; 55. DR MINT; P0AES4; -. DR STRING; 511145.b2231; -. DR BindingDB; P0AES4; -. DR ChEMBL; CHEMBL1858; -. DR DrugBank; DB00537; Ciprofloxacin. DR DrugBank; DB11943; Delafloxacin. DR DrugBank; DB12134; Gepotidacin. DR DrugBank; DB00779; Nalidixic acid. DR DrugBank; DB13823; Pipemidic acid. DR DrugCentral; P0AES4; -. DR jPOST; P0AES4; -. DR PaxDb; 511145-b2231; -. DR EnsemblBacteria; AAC75291; AAC75291; b2231. DR GeneID; 75206476; -. DR GeneID; 946614; -. DR KEGG; ecj:JW2225; -. DR KEGG; eco:b2231; -. DR KEGG; ecoc:C3026_12465; -. DR PATRIC; fig|1411691.4.peg.4; -. DR EchoBASE; EB0418; -. DR eggNOG; COG0188; Bacteria. DR HOGENOM; CLU_002977_6_1_6; -. DR InParanoid; P0AES4; -. DR OMA; THHWLLF; -. DR OrthoDB; 9806486at2; -. DR PhylomeDB; P0AES4; -. DR BioCyc; EcoCyc:EG10423-MONOMER; -. DR BioCyc; MetaCyc:EG10423-MONOMER; -. DR Reactome; R-HSA-9638771; Action of antimicrobials. DR Reactome; R-HSA-9913143; Antimicrobial resistance. DR EvolutionaryTrace; P0AES4; -. DR PRO; PR:P0AES4; -. DR Proteomes; UP000000625; Chromosome. DR AbasyAtlas; P0AES4; -. DR GO; GO:0005694; C:chromosome; IEA:InterPro. DR GO; GO:0005737; C:cytoplasm; IDA:EcoliWiki. DR GO; GO:0005829; C:cytosol; IDA:EcoCyc. DR GO; GO:0009330; C:DNA topoisomerase type II (double strand cut, ATP-hydrolyzing) complex; IBA:GO_Central. DR GO; GO:0016020; C:membrane; HDA:UniProtKB. DR GO; GO:0005524; F:ATP binding; IBA:GO_Central. DR GO; GO:0008094; F:ATP-dependent activity, acting on DNA; IDA:EcoliWiki. DR GO; GO:0003677; F:DNA binding; IDA:EcoliWiki. 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:CACAO. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0006265; P:DNA topological change; IMP:EcoliWiki. DR GO; GO:0006261; P:DNA-templated DNA replication; IEA:UniProtKB-UniRule. DR GO; GO:0006351; P:DNA-templated transcription; IDA:EcoliWiki. DR GO; GO:2000104; P:negative regulation of DNA-templated DNA replication; IDA:ComplexPortal. DR GO; GO:0009410; P:response to xenobiotic stimulus; IMP:EcoliWiki. DR CDD; cd00187; TOP4c; 1. DR FunFam; 2.120.10.90:FF:000002; DNA gyrase subunit A; 1. DR FunFam; 3.30.1360.40:FF:000002; DNA gyrase subunit A; 1. DR FunFam; 3.90.199.10:FF:000001; DNA gyrase subunit A; 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 InterPro; IPR050220; Type_II_DNA_Topoisomerases. DR NCBIfam; TIGR01063; gyrA; 1. DR NCBIfam; NF004043; PRK05560.1; 1. DR NCBIfam; NF004044; PRK05561.1; 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; PS52040; TOPO_IIA; 1. DR PDBsum; 1AB4; -. DR PDBsum; 1X75; -. DR PDBsum; 1ZI0; -. DR PDBsum; 2Y3P; -. DR PDBsum; 3NUH; -. DR PDBsum; 4ELY; -. DR PDBsum; 6RKS; -. DR PDBsum; 6RKU; -. DR PDBsum; 6RKV; -. DR PDBsum; 6RKW; -. DR PDBsum; 7Z9C; -. DR PDBsum; 7Z9G; -. DR PDBsum; 7Z9K; -. DR PDBsum; 7Z9M; -. DR PDBsum; 8QDX; -. DR PDBsum; 8QQI; -. DR PDBsum; 8QQS; -. DR PDBsum; 8QQU; -. DR PDBsum; 9GBV; -. DR PDBsum; 9GGQ; -. PE 1: Evidence at protein level; KW 3D-structure; Antibiotic resistance; ATP-binding; Cytoplasm; KW Direct protein sequencing; DNA-binding; Isomerase; Nucleotide-binding; KW Reference proteome; Topoisomerase. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0000269|PubMed:3029031" FT CHAIN 2..875 FT /note="DNA gyrase subunit A" FT /id="PRO_0000145232" FT DOMAIN 34..533 FT /note="Topo IIA-type catalytic" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01384" FT REGION 531..841 FT /note="C-terminal domain (CTD)" FT /evidence="ECO:0000303|PubMed:15897198" FT REGION 841..875 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 842..875 FT /note="Acidic tail" FT /evidence="ECO:0000303|PubMed:22457353" FT MOTIF 560..566 FT /note="GyrA-box" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01897, FT ECO:0000303|PubMed:9426128" FT COMPBIAS 857..875 FT /note="Acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 122 FT /note="O-(5'-phospho-DNA)-tyrosine intermediate" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01897, FT ECO:0000269|PubMed:3031051" FT VARIANT 67 FT /note="A -> S (in PPA-10; quinolone-resistant)" FT /evidence="ECO:0000269|PubMed:2168148" FT VARIANT 81 FT /note="G -> C (in NAL-97; quinolone-resistant)" FT /evidence="ECO:0000269|PubMed:2168148" FT VARIANT 83 FT /note="S -> L (in NAL-51, NAL-112, NAL-118, NAL-119 and FT strains 58, 158, 218, 231 and 235; quinolone-resistant)" FT /evidence="ECO:0000269|PubMed:1850972, FT ECO:0000269|PubMed:2168148" FT VARIANT 83 FT /note="S -> W (in PPA-18 and strains 233 and 227; FT quinolone-resistant)" FT /evidence="ECO:0000269|PubMed:1850972, FT ECO:0000269|PubMed:2168148, ECO:0000269|PubMed:2548439" FT VARIANT 84 FT /note="A -> P (in PPA-05; quinolone-resistant)" FT /evidence="ECO:0000269|PubMed:2168148" FT VARIANT 87 FT /note="D -> N (in NAL-113 and OV6; quinolone-resistant)" FT /evidence="ECO:0000269|PubMed:2168148, FT ECO:0000269|PubMed:2834621" FT VARIANT 87 FT /note="D -> V (in strain: 202; partially FT quinolone-resistant)" FT /evidence="ECO:0000269|PubMed:1850972" FT VARIANT 106 FT /note="Q -> H (in NAL-89; quinolone-resistant)" FT /evidence="ECO:0000269|PubMed:2168148" FT VARIANT 678 FT /note="D -> E (in strain: 227)" FT /evidence="ECO:0000269|PubMed:2548439" FT VARIANT 798 FT /note="I -> IMMI (in strain: OV6; quinolone-resistant)" FT /evidence="ECO:0000269|PubMed:2834621" FT VARIANT 828 FT /note="A -> S (in strain: 227)" FT /evidence="ECO:0000269|PubMed:2548439" FT MUTAGEN 32 FT /note="R->A,Q: Nearly abolishes DNA supercoiling. Reduces FT quinolone-induced DNA cleavage and relaxation." FT /evidence="ECO:0000269|PubMed:12051842" FT MUTAGEN 47 FT /note="R->Q: Nearly abolishes DNA supercoiling. Reduces FT quinolone-induced DNA cleavage. Slightly reduces DNA FT relaxation." FT /evidence="ECO:0000269|PubMed:12051842" FT MUTAGEN 78 FT /note="H->A: Nearly abolishes DNA supercoiling. Reduces FT quinolone-induced DNA cleavage and DNA relaxation." FT /evidence="ECO:0000269|PubMed:12051842" FT MUTAGEN 80 FT /note="H->A: Reduces DNA supercoiling. Slightly reduces FT quinolone-induced DNA cleavage. No effect on DNA FT relaxation." FT /evidence="ECO:0000269|PubMed:12051842" FT MUTAGEN 83 FT /note="S->A: Resistant to fluoroquinolones." FT /evidence="ECO:0000269|PubMed:1850970" FT MUTAGEN 106 FT /note="Q->R: Resistant to fluoroquinolones." FT /evidence="ECO:0000269|PubMed:1850970" FT MUTAGEN 462 FT /note="R->C: In gyrA462; resistant to cytotoxic protein FT CcdB, but not to the quinoline antibiotic enoxacin, has no FT effect on DNA supercoiling. Does not interact with CcdB." FT /evidence="ECO:0000269|PubMed:1324324, FT ECO:0000269|PubMed:8254658" FT MUTAGEN 560..566 FT /note="QRRGGKG->AAAAAAA: Loss of gyrase-mediated DNA FT wrapping, nearly complete loss of DNA supercoiling FT activity, no change in DNA supercoil relaxation or DNA FT decatenation activity." FT /evidence="ECO:0000269|PubMed:16332690" FT MUTAGEN 560..566 FT /note="Missing: Loss of gyrase-mediated DNA wrapping, FT nearly complete loss of DNA supercoiling activity, no FT change in DNA supercoil relaxation or DNA decatenation FT activity." FT /evidence="ECO:0000269|PubMed:16332690" FT MUTAGEN 842..856 FT /note="Missing: Gains ability to wrap DNA around itself in FT the absence of GyrB; holoenzyme gains ability to wrap DNA FT in the absence of ATP analogs, but reduces ATP-dependent FT supercoiling activity 50-fold, DNA is not as extensively FT negatively supercoiled, has 10-fold less ATP-independent FT negative supercoiled DNA relaxation activity, no change in FT ATPase activity of holoenzyme, no change in decatenation FT ability. Isolated CTD gains ability to wrap DNA around FT itself in the absence of GyrB, binds DNA better than FT wild-type CTD." FT /evidence="ECO:0000269|PubMed:22457352, FT ECO:0000269|PubMed:22457353" FT MUTAGEN 854..875 FT /note="Missing: Isolated CTD gains ability to wrap DNA FT around itself in the absence of GyrB, binds DNA better than FT wild-type CTD." FT /evidence="ECO:0000269|PubMed:22457353" FT STRAND 8..12 FT /evidence="ECO:0007829|PDB:9GBV" FT HELIX 13..28 FT /evidence="ECO:0007829|PDB:9GBV" FT HELIX 29..33 FT /evidence="ECO:0007829|PDB:9GBV" FT TURN 37..39 FT /evidence="ECO:0007829|PDB:9GBV" FT HELIX 43..54 FT /evidence="ECO:0007829|PDB:9GBV" FT STRAND 59..61 FT /evidence="ECO:0007829|PDB:1AB4" FT HELIX 66..76 FT /evidence="ECO:0007829|PDB:9GBV" FT HELIX 83..91 FT /evidence="ECO:0007829|PDB:9GBV" FT TURN 95..97 FT /evidence="ECO:0007829|PDB:9GBV" FT STRAND 102..107 FT /evidence="ECO:0007829|PDB:9GBV" FT HELIX 115..119 FT /evidence="ECO:0007829|PDB:9GBV" FT TURN 120..122 FT /evidence="ECO:0007829|PDB:9GBV" FT STRAND 124..127 FT /evidence="ECO:0007829|PDB:9GBV" FT HELIX 130..133 FT /evidence="ECO:0007829|PDB:9GBV" FT TURN 134..139 FT /evidence="ECO:0007829|PDB:9GBV" FT STRAND 145..147 FT /evidence="ECO:0007829|PDB:9GBV" FT STRAND 149..158 FT /evidence="ECO:0007829|PDB:9GBV" FT HELIX 165..169 FT /evidence="ECO:0007829|PDB:9GBV" FT STRAND 171..174 FT /evidence="ECO:0007829|PDB:9GBV" FT STRAND 179..182 FT /evidence="ECO:0007829|PDB:9GBV" FT HELIX 187..200 FT /evidence="ECO:0007829|PDB:9GBV" FT HELIX 205..209 FT /evidence="ECO:0007829|PDB:9GBV" FT STRAND 222..224 FT /evidence="ECO:0007829|PDB:9GBV" FT HELIX 229..235 FT /evidence="ECO:0007829|PDB:9GBV" FT STRAND 236..243 FT /evidence="ECO:0007829|PDB:9GBV" FT STRAND 245..250 FT /evidence="ECO:0007829|PDB:9GBV" FT STRAND 252..254 FT /evidence="ECO:0007829|PDB:9GBV" FT STRAND 257..263 FT /evidence="ECO:0007829|PDB:9GBV" FT HELIX 270..282 FT /evidence="ECO:0007829|PDB:9GBV" FT STRAND 288..294 FT /evidence="ECO:0007829|PDB:9GBV" FT STRAND 298..300 FT /evidence="ECO:0007829|PDB:1AB4" FT STRAND 303..307 FT /evidence="ECO:0007829|PDB:9GBV" FT HELIX 313..323 FT /evidence="ECO:0007829|PDB:9GBV" FT STRAND 327..333 FT /evidence="ECO:0007829|PDB:9GBV" FT STRAND 335..338 FT /evidence="ECO:0007829|PDB:9GBV" FT STRAND 341..344 FT /evidence="ECO:0007829|PDB:9GBV" FT HELIX 347..386 FT /evidence="ECO:0007829|PDB:9GBV" FT HELIX 390..398 FT /evidence="ECO:0007829|PDB:9GBV" FT STRAND 400..402 FT /evidence="ECO:0007829|PDB:1X75" FT HELIX 403..410 FT /evidence="ECO:0007829|PDB:9GBV" FT STRAND 411..413 FT /evidence="ECO:0007829|PDB:8QQI" FT HELIX 418..420 FT /evidence="ECO:0007829|PDB:9GBV" FT HELIX 421..425 FT /evidence="ECO:0007829|PDB:9GBV" FT HELIX 429..431 FT /evidence="ECO:0007829|PDB:9GBV" FT STRAND 435..437 FT /evidence="ECO:0007829|PDB:7Z9G" FT STRAND 441..449 FT /evidence="ECO:0007829|PDB:9GBV" FT HELIX 452..459 FT /evidence="ECO:0007829|PDB:9GBV" FT HELIX 463..466 FT /evidence="ECO:0007829|PDB:9GBV" FT HELIX 468..493 FT /evidence="ECO:0007829|PDB:9GBV" FT HELIX 495..513 FT /evidence="ECO:0007829|PDB:9GBV" FT STRAND 520..522 FT /evidence="ECO:0007829|PDB:9GGQ" FT HELIX 523..526 FT /evidence="ECO:0007829|PDB:9GGQ" FT STRAND 530..534 FT /evidence="ECO:0007829|PDB:9GGQ" FT STRAND 538..546 FT /evidence="ECO:0007829|PDB:9GBV" FT STRAND 549..553 FT /evidence="ECO:0007829|PDB:9GBV" FT HELIX 554..556 FT /evidence="ECO:0007829|PDB:9GBV" FT TURN 563..565 FT /evidence="ECO:0007829|PDB:8QDX" FT STRAND 578..587 FT /evidence="ECO:0007829|PDB:9GBV" FT STRAND 589..593 FT /evidence="ECO:0007829|PDB:9GBV" FT STRAND 597..603 FT /evidence="ECO:0007829|PDB:9GBV" FT HELIX 604..606 FT /evidence="ECO:0007829|PDB:9GBV" FT STRAND 612..614 FT /evidence="ECO:0007829|PDB:1ZI0" FT HELIX 619..621 FT /evidence="ECO:0007829|PDB:9GBV" FT STRAND 633..638 FT /evidence="ECO:0007829|PDB:9GBV" FT STRAND 645..650 FT /evidence="ECO:0007829|PDB:9GBV" FT STRAND 653..659 FT /evidence="ECO:0007829|PDB:9GBV" FT HELIX 660..663 FT /evidence="ECO:0007829|PDB:9GBV" FT STRAND 671..674 FT /evidence="ECO:0007829|PDB:1ZI0" FT STRAND 682..688 FT /evidence="ECO:0007829|PDB:9GBV" FT STRAND 693..698 FT /evidence="ECO:0007829|PDB:9GBV" FT STRAND 701..707 FT /evidence="ECO:0007829|PDB:9GBV" FT HELIX 708..710 FT /evidence="ECO:0007829|PDB:9GBV" FT STRAND 732..736 FT /evidence="ECO:0007829|PDB:9GBV" FT STRAND 740..742 FT /evidence="ECO:0007829|PDB:9GGQ" FT STRAND 743..748 FT /evidence="ECO:0007829|PDB:9GBV" FT STRAND 751..753 FT /evidence="ECO:0007829|PDB:9GBV" FT HELIX 758..760 FT /evidence="ECO:0007829|PDB:9GBV" FT STRAND 766..768 FT /evidence="ECO:0007829|PDB:9GBV" FT STRAND 771..774 FT /evidence="ECO:0007829|PDB:1ZI0" FT TURN 777..780 FT /evidence="ECO:0007829|PDB:9GBV" FT STRAND 783..789 FT /evidence="ECO:0007829|PDB:9GBV" FT STRAND 794..799 FT /evidence="ECO:0007829|PDB:9GBV" FT STRAND 802..809 FT /evidence="ECO:0007829|PDB:9GBV" FT HELIX 811..813 FT /evidence="ECO:0007829|PDB:8QDX" FT STRAND 817..819 FT /evidence="ECO:0007829|PDB:9GBV" FT STRAND 833..839 FT /evidence="ECO:0007829|PDB:9GBV" SQ SEQUENCE 875 AA; 96964 MW; 3FD5BD52A5969069 CRC64; MSDLAREITP VNIEEELKSS YLDYAMSVIV GRALPDVRDG LKPVHRRVLY AMNVLGNDWN KAYKKSARVV GDVIGKYHPH GDSAVYDTIV RMAQPFSLRY MLVDGQGNFG SIDGDSAAAM RYTEIRLAKI AHELMADLEK ETVDFVDNYD GTEKIPDVMP TKIPNLLVNG SSGIAVGMAT NIPPHNLTEV INGCLAYIDD EDISIEGLME HIPGPDFPTA AIINGRRGIE EAYRTGRGKV YIRARAEVEV DAKTGRETII VHEIPYQVNK ARLIEKIAEL VKEKRVEGIS ALRDESDKDG MRIVIEVKRD AVGEVVLNNL YSQTQLQVSF GINMVALHHG QPKIMNLKDI IAAFVRHRRE VVTRRTIFEL RKARDRAHIL EALAVALANI DPIIELIRHA PTPAEAKTAL VANPWQLGNV AAMLERAGDD AARPEWLEPE FGVRDGLYYL TEQQAQAILD LRLQKLTGLE HEKLLDEYKE LLDQIAELLR ILGSADRLME VIREELELVR EQFGDKRRTE ITANSADINL EDLITQEDVV VTLSHQGYVK YQPLSEYEAQ RRGGKGKSAA RIKEEDFIDR LLVANTHDHI LCFSSRGRVY SMKVYQLPEA TRGARGRPIV NLLPLEQDER ITAILPVTEF EEGVKVFMAT ANGTVKKTVL TEFNRLRTAG KVAIKLVDGD ELIGVDLTSG EDEVMLFSAE GKVVRFKESS VRAMGCNTTG VRGIRLGEGD KVVSLIVPRG DGAILTATQN GYGKRTAVAE YPTKSRATKG VISIKVTERN GLVVGAVQVD DCDQIMMITD AGTLVRTRVS EISIVGRNTQ GVILIRTAED ENVVGLQRVA EPVDEEDLDT IDGSAAEGDD EIAPEVDVDD EPEEE //