General Information of the Molecule (ID: Mol02146)
Name
DNA gyrase subunit A (GYRA) ,Clostridioides difficile
Synonyms
gyrA CD630_00060
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Molecule Type
Protein
Gene Name
gyrA
Gene ID
66352444
Sequence
MEENNKILPIEIAEEMKKSYIDYSMSVIAGRALPDVRDGLKPVHRRILYSMSELNLTPDK
PYRKSARIVGDVLGKYHPHGDTAVYYAMVRMAQDFSTRALLVDGHGNFGSVDGDSPAAMR
YTEAKMSKLSLELLRDIEKETVDFKPNFDESLKEPSVLPARYPNLLVNGSNGIAVGMATS
IPPHNLAEVIDATVYLIDNPECSVDDLIKFVQGPDFPTAAIIMGKESIAEAYRTGRGKVK
VRSRAFIEELPKGKQQIIVTEIPYQVNKAKLVERIAELVKEKRIEGISDLRDESNRNGMR
IVIELKRDANANIVLNNLYKHSQMEDTFSIIMLALVDGQPRVLNLKQILYHYIKHQEDVV
TRRTKFELNKAEARAHILEGLKIALDNIDAVISLIRASKTGQEAKLGLIEKFKLTEIQAQ
AILDMRLQRLTGLERDKIEAEYEDLIKKINRLKEILADERLLLNVIKDEITIIKENYSDE
RRTEIRHAEGEIDMRDLISDEEIAITLTHFGYIKRLPSDTYKSQKRGGRGISALTTREED
FVRHLVTTTTHSRLLFFTNKGRVFKLNAYEIPEGKRQAKGTAIVNLLQLSADEKIATLIP
IDGNDENEYLLLATKKGIVKKTKREEFKNINKSGLIAIGLRDDDELIGVELTDGKQEVLL
VTKEGMSIRFDENDIRYMGRTAMGVKGITLSKEDFVVSMNLCSKGTDVLVVSKNGFGKRT
NIEEYRSQIRAGKGIKTYNISEKTGTIVGADMVNEDDEIMIINSDGVLIRIRVNEISLFG
RVTSGVKLMKTNDEVNVVSIAKINIEEE
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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.
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Uniprot ID
Q18C90_CLOD6
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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
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Ciprofloxacin XR
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Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Aberration of the Drug's Therapeutic Target (ADTT) Click to Show/Hide
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
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Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Aberration of the Drug's Therapeutic Target (ADTT) Click to Show/Hide
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

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