| IED ID | IndEnz0002003204 |
| Enzyme Type ID | protease003204 |
| Protein Name |
DNA gyrase subunit A EC 5.6.2.2 Type IIA topoisomerase subunit GyrA |
| Gene Name | gyrA Rv0006 MTCY10H4.04 |
| Organism | Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv) |
| Taxonomic Lineage | cellular organisms Bacteria Terrabacteria group Actinobacteria Actinomycetia (high G+C Gram-positive bacteria) Corynebacteriales Mycobacteriaceae Mycobacterium Mycobacterium tuberculosis complex Mycobacterium tuberculosis Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv) |
| Enzyme Sequence | MTDTTLPPDDSLDRIEPVDIEQEMQRSYIDYAMSVIVGRALPEVRDGLKPVHRRVLYAMFDSGFRPDRSHAKSARSVAETMGNYHPHGDASIYDSLVRMAQPWSLRYPLVDGQGNFGSPGNDPPAAMRYTEARLTPLAMEMLREIDEETVDFIPNYDGRVQEPTVLPSRFPNLLANGSGGIAVGMATNIPPHNLRELADAVFWALENHDADEEETLAAVMGRVKGPDFPTAGLIVGSQGTADAYKTGRGSIRMRGVVEVEEDSRGRTSLVITELPYQVNHDNFITSIAEQVRDGKLAGISNIEDQSSDRVGLRIVIEIKRDAVAKVVINNLYKHTQLQTSFGANMLAIVDGVPRTLRLDQLIRYYVDHQLDVIVRRTTYRLRKANERAHILRGLVKALDALDEVIALIRASETVDIARAGLIELLDIDEIQAQAILDMQLRRLAALERQRIIDDLAKIEAEIADLEDILAKPERQRGIVRDELAEIVDRHGDDRRTRIIAADGDVSDEDLIAREDVVVTITETGYAKRTKTDLYRSQKRGGKGVQGAGLKQDDIVAHFFVCSTHDLILFFTTQGRVYRAKAYDLPEASRTARGQHVANLLAFQPEERIAQVIQIRGYTDAPYLVLATRNGLVKKSKLTDFDSNRSGGIVAVNLRDNDELVGAVLCSAGDDLLLVSANGQSIRFSATDEALRPMGRATSGVQGMRFNIDDRLLSLNVVREGTYLLVATSGGYAKRTAIEEYPVQGRGGKGVLTVMYDRRRGRLVGALIVDDDSELYAVTSGGGVIRTAARQVRKAGRQTKGVRLMNLGEGDTLLAIARNAEESGDDNAVDANGADQTGN |
| Enzyme Length | 838 |
| Uniprot Accession Number | P9WG47 |
| Absorption | |
| Active Site | ACT_SITE 129; /note=O-(5'-phospho-DNA)-tyrosine intermediate; /evidence=ECO:0000255|HAMAP-Rule:MF_01897 |
| Activity Regulation | ACTIVITY REGULATION: DNA supercoiling inhibited by (fluoro)quinoline antibiotics such as sparfloxacin and levofloxacin, which usually act on GyrA (PubMed:15047530, PubMed:17015625). DNA supercoiling inhibited by the coumarin antibiotic novobiocin which acts on GyrB (PubMed:16876125). Quinolones lead to gyrase-mediated dsDNA cleavage while preventing reclosure (PubMed:15047530, PubMed:16876125, PubMed:23869946). DNA supercoiling activity inhibited by aminopyrazinamide and pyrrolamide derivatives, probably via effects on the GyrB subunit (PubMed:23268609, PubMed:24126580). DNA relaxation inhibited by ATP and its analogs (PubMed:16876125). DNA supercoiling, relaxation, decatenation and quinolone-promoted DNA cleavage are inhibited by MfpA (50% inhibition occurs at 2 uM), inhibition of gyrase activities is enhanced in a concentration-dependent manner by MfpA (PubMed:19060136). {ECO:0000269|PubMed:15047530, ECO:0000269|PubMed:16876125, ECO:0000269|PubMed:17015625, ECO:0000269|PubMed:19060136, ECO:0000269|PubMed:23268609, ECO:0000269|PubMed:23869946, ECO:0000269|PubMed:24126580}. |
| Binding Site | |
| Calcium Binding | CA_BIND 504..516; /evidence=ECO:0000305|PubMed:22844097 |
| catalytic Activity | CATALYTIC ACTIVITY: Reaction=ATP-dependent breakage, passage and rejoining of double-stranded DNA.; EC=5.6.2.2; Evidence={ECO:0000255|HAMAP-Rule:MF_01897, ECO:0000269|PubMed:15047530, ECO:0000269|PubMed:16876125}; |
| DNA Binding | |
| EC Number | 5.6.2.2 |
| Enzyme Function | FUNCTION: A type II topoisomerase that negatively supercoils closed circular double-stranded (ds) DNA in an ATP-dependent manner to maintain chromosomes in an underwound state, while in the absence of ATP it relaxes supercoiled dsDNA (PubMed:15047530, PubMed:16377674, PubMed:16876125, PubMed:17015625, PubMed:18426901, PubMed:19060136, PubMed:22844097, PubMed:20805881). Also catalyzes the interconversion of other topological isomers of dsDNA rings, including catenanes (PubMed:16876125, PubMed:19060136, PubMed:22457352). Gyrase from M.tuberculosis has higher decatenation than supercoiling activity compared to E.coli; as M.tuberculosis only has 1 type II topoisomerase, gyrase has to fulfill the decatenation function of topoisomerase IV as well (PubMed:16876125, PubMed:22457352, PubMed:23869946). At comparable concentrations M.tuberculosis gyrase cannot introduce as many negative supercoils into DNA as the E.coli enzyme, and its ATPase activity is lower, perhaps because it does not couple DNA wrapping and ATP binding as well as E.coli (PubMed:22457352). {ECO:0000269|PubMed:15047530, ECO:0000269|PubMed:16377674, ECO:0000269|PubMed:16876125, ECO:0000269|PubMed:17015625, ECO:0000269|PubMed:18426901, ECO:0000269|PubMed:19060136, ECO:0000269|PubMed:20805881, ECO:0000269|PubMed:22457352, ECO:0000269|PubMed:22844097, ECO:0000269|PubMed:23869946}.; FUNCTION: Negative supercoiling favors strand separation, and DNA replication, transcription, recombination and repair, all of which involve strand separation. Type II topoisomerases break and join 2 DNA strands simultaneously in an ATP-dependent manner. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Active site (1); Beta strand (45); Calcium binding (1); Chain (1); Domain (1); Helix (27); Initiator methionine (1); Modified residue (1); Motif (2); Mutagenesis (22); Natural variant (7); Region (1); Sequence conflict (2); Turn (7) |
| Keywords | 3D-structure;ATP-binding;Acetylation;Antibiotic resistance;Calcium;Cytoplasm;DNA-binding;Isomerase;Nucleotide-binding;Reference proteome;Topoisomerase |
| Interact With | |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: Cytoplasm {ECO:0000255|HAMAP-Rule:MF_01897}. |
| Modified Residue | MOD_RES 2; /note=N-acetylthreonine; /evidence=ECO:0007744|PubMed:21969609 |
| Post Translational Modification | |
| Signal Peptide | |
| Structure 3D | X-ray crystallography (15) |
| Cross Reference PDB | 3IFZ; 3ILW; 3UC1; 4G3N; 5BS8; 5BTA; 5BTC; 5BTD; 5BTF; 5BTG; 5BTI; 5BTL; 5BTN; 6GAU; 6GAV; |
| Mapped Pubmed ID | 26792525; 30744994; |
| Motif | MOTIF 537..543; /note="GyrA-box"; /evidence="ECO:0000255|HAMAP-Rule:MF_01897, ECO:0000303|PubMed:23869946"; MOTIF 743..749; /note="GyrA-box-1"; /evidence="ECO:0000303|PubMed:23869946" |
| Gene Encoded By | |
| Mass | 92,274 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | |
| Cross Reference Brenda | 5.6.2.2; |