Molecule Information

General Information of the Molecule (ID: Mol02146)

• Name: DNA gyrase subunit A (GYRA) ,Clostridioides difficile
• Synonyms: gyrA CD630_00060
• Molecule Type: Protein
• Gene Name: gyrA
• Gene ID: 66352444
• Sequence:
  MEENNKILPIEIAEEMKKSYIDYSMSVIAGRALPDVRDGLKPVHRRILYSMSELNLTPDK
  PYRKSARIVGDVLGKYHPHGDTAVYYAMVRMAQDFSTRALLVDGHGNFGSVDGDSPAAMR
  YTEAKMSKLSLELLRDIEKETVDFKPNFDESLKEPSVLPARYPNLLVNGSNGIAVGMATS
  IPPHNLAEVIDATVYLIDNPECSVDDLIKFVQGPDFPTAAIIMGKESIAEAYRTGRGKVK
  VRSRAFIEELPKGKQQIIVTEIPYQVNKAKLVERIAELVKEKRIEGISDLRDESNRNGMR
  IVIELKRDANANIVLNNLYKHSQMEDTFSIIMLALVDGQPRVLNLKQILYHYIKHQEDVV
  TRRTKFELNKAEARAHILEGLKIALDNIDAVISLIRASKTGQEAKLGLIEKFKLTEIQAQ
  AILDMRLQRLTGLERDKIEAEYEDLIKKINRLKEILADERLLLNVIKDEITIIKENYSDE
  RRTEIRHAEGEIDMRDLISDEEIAITLTHFGYIKRLPSDTYKSQKRGGRGISALTTREED
  FVRHLVTTTTHSRLLFFTNKGRVFKLNAYEIPEGKRQAKGTAIVNLLQLSADEKIATLIP
  IDGNDENEYLLLATKKGIVKKTKREEFKNINKSGLIAIGLRDDDELIGVELTDGKQEVLL
  VTKEGMSIRFDENDIRYMGRTAMGVKGITLSKEDFVVSMNLCSKGTDVLVVSKNGFGKRT
  NIEEYRSQIRAGKGIKTYNISEKTGTIVGADMVNEDDEIMIINSDGVLIRIRVNEISLFG
  RVTSGVKLMKTNDEVNVVSIAKINIEEE
• Function: A type II topoisomerase that negatively supercoils closed circular double-stranded (ds) DNA in an ATP-dependent manner to modulate DNA topology and maintain chromosomes in an underwound state. Negative supercoiling favors strand separation, and DNA replication, transcription, recombination and repair, all of which involve strand separation. Also able to catalyze the interconversion of other topological isomers of dsDNA rings, including catenanes and knotted rings. Type II topoisomerases break and join 2 DNA strands simultaneously in an ATP-dependent manner.
• Uniprot ID: Q18C90_CLOD6

Kingdom: N.A.
Phylum: Firmicutes
Class: Clostridia
Order: Eubacteriales
Family: Peptostreptococcaceae
Genus: Clostridioides
Species: Clostridioides difficile

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) 2 drug(s) in total

Ciprofloxacin XR

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Clostridium difficile infection [1]

• Resistant Disease: Clostridium difficile infection [ICD-11: 1A04.0]
• Resistant Drug: Ciprofloxacin XR
• Molecule Alteration: Mutation; p.T82I
• Experimental Note: Discovered Using In-vivo Testing Model
• Mechanism Description: Mutations in the gyrA or gyrB gene within quinolone resistance-determining region lead to the reduction in fidelity or prevention of drug binding via the target conformation change. Although several amino acid substitutions have been noted in GyrA and/or GyrB, the most frequent amino acid change has been recognized at T82I in GyrA subunit.

Ofloxacin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Clostridium difficile infection [1]

• Resistant Disease: Clostridium difficile infection [ICD-11: 1A04.0]
• Resistant Drug: Ofloxacin
• Molecule Alteration: Mutation; p.T82I
• Experimental Note: Discovered Using In-vivo Testing Model
• Mechanism Description: Mutations in the gyrA or gyrB gene within quinolone resistance-determining region lead to the reduction in fidelity or prevention of drug binding via the target conformation change. Although several amino acid substitutions have been noted in GyrA and/or GyrB, the most frequent amino acid change has been recognized at T82I in GyrA subunit.

References

• Ref 1: Insights into drug resistance mechanisms in Clostridium difficile .Essays Biochem. 2017 Mar 3;61(1):81-88. doi: 10.1042/EBC20160062. Print 2017 Feb 28. 10.1042/EBC20160062