Molecule Information

General Information of the Molecule (ID: Mol02000)

• Name: DNA gyrase subunit A (GYRA) ,Mycobacterium tuberculosis
• Synonyms: gyrA; Rv0006; MTCY10H4.04
• Molecule Type: Protein
• Gene Name: GYRA
• Gene ID: 887105
• Sequence:
  MTDTTLPPDDSLDRIEPVDIEQEMQRSYIDYAMSVIVGRALPEVRDGLKPVHRRVLYAMF
  DSGFRPDRSHAKSARSVAETMGNYHPHGDASIYDSLVRMAQPWSLRYPLVDGQGNFGSPG
  NDPPAAMRYTEARLTPLAMEMLREIDEETVDFIPNYDGRVQEPTVLPSRFPNLLANGSGG
  IAVGMATNIPPHNLRELADAVFWALENHDADEEETLAAVMGRVKGPDFPTAGLIVGSQGT
  ADAYKTGRGSIRMRGVVEVEEDSRGRTSLVITELPYQVNHDNFITSIAEQVRDGKLAGIS
  NIEDQSSDRVGLRIVIEIKRDAVAKVVINNLYKHTQLQTSFGANMLAIVDGVPRTLRLDQ
  LIRYYVDHQLDVIVRRTTYRLRKANERAHILRGLVKALDALDEVIALIRASETVDIARAG
  LIELLDIDEIQAQAILDMQLRRLAALERQRIIDDLAKIEAEIADLEDILAKPERQRGIVR
  DELAEIVDRHGDDRRTRIIAADGDVSDEDLIAREDVVVTITETGYAKRTKTDLYRSQKRG
  GKGVQGAGLKQDDIVAHFFVCSTHDLILFFTTQGRVYRAKAYDLPEASRTARGQHVANLL
  AFQPEERIAQVIQIRGYTDAPYLVLATRNGLVKKSKLTDFDSNRSGGIVAVNLRDNDELV
  GAVLCSAGDDLLLVSANGQSIRFSATDEALRPMGRATSGVQGMRFNIDDRLLSLNVVREG
  TYLLVATSGGYAKRTAIEEYPVQGRGGKGVLTVMYDRRRGRLVGALIVDDDSELYAVTSG
  GGVIRTAARQVRKAGRQTKGVRLMNLGEGDTLLAIARNAEESGDDNAVDANGADQTGN
• 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. Also catalyzes the interconversion of other topological isomers of dsDNA rings, including catenanes. 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. 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.
• Uniprot ID: GYRA_MYCTU

Kingdom: N.A.
Phylum: Actinobacteria
Class: Actinomycetia
Order: 85007
Family: Mycobacteriaceae
Genus: Mycobacterium
Species: Mycobacterium tuberculosis

Type(s) of Resistant Mechanism of This Molecule

  ADTT: Aberration of the Drug's Therapeutic Target

Drug Resistance Data Categorized by Drug

Approved Drug(s) 1 drug(s) in total

Gatifloxacin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Mycolicibacterium smegmatis infection [1]

• Resistant Disease: Mycolicibacterium smegmatis infection [ICD-11: 1B2Z.6]
• Resistant Drug: Gatifloxacin
• Molecule Alteration: Missense mutation; p.G280A (c.D94N)
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: STK11 KO cells; Fetal kidney; Homo sapiens (Human); CVCL_B3IE
• Experiment for Molecule Alteration: Whole-genome sequencing assay
• Mechanism Description: Mutations in the gyrA and gyrB genes are the main mechanisms of Gatifloxacin (GAT) resistance.

Disease Class: Mycolicibacterium smegmatis infection [1]

• Resistant Disease: Mycolicibacterium smegmatis infection [ICD-11: 1B2Z.6]
• Resistant Drug: Gatifloxacin
• Molecule Alteration: Missense mutation; p.A281G (c.D94G)
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: STK11 KO cells; Fetal kidney; Homo sapiens (Human); CVCL_B3IE
• Experiment for Molecule Alteration: Whole-genome sequencing assay
• Mechanism Description: Mutations in the gyrA and gyrB genes are the main mechanisms of Gatifloxacin (GAT) resistance.

Disease Class: Mycolicibacterium smegmatis infection [1]

• Resistant Disease: Mycolicibacterium smegmatis infection [ICD-11: 1B2Z.6]
• Resistant Drug: Gatifloxacin
• Molecule Alteration: Missense mutation; p.G280T (c.D94Y)
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: STK11 KO cells; Fetal kidney; Homo sapiens (Human); CVCL_B3IE
• Experiment for Molecule Alteration: Whole-genome sequencing assay
• Mechanism Description: Mutations in the gyrA and gyrB genes are the main mechanisms of Gatifloxacin (GAT) resistance.

Disease Class: Mycolicibacterium smegmatis infection [1]

• Resistant Disease: Mycolicibacterium smegmatis infection [ICD-11: 1B2Z.6]
• Resistant Drug: Gatifloxacin
• Molecule Alteration: Missense mutation; p.G262T (c.G88C)
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: STK11 KO cells; Fetal kidney; Homo sapiens (Human); CVCL_B3IE
• Experiment for Molecule Alteration: Whole-genome sequencing assay
• Mechanism Description: Mutations in the gyrA and gyrB genes are the main mechanisms of Gatifloxacin (GAT) resistance.

References

• Ref 1: Characterizing the gene mutations associated with resistance to gatifloxacin in Mycobacterium tuberculosis through whole-genome sequencing .Int J Infect Dis. 2021 Nov;112:189-194. doi: 10.1016/j.ijid.2021.09.028. Epub 2021 Sep 20. 10.1016/j.ijid.2021.09.028