Molecule Information

General Information of the Molecule (ID: Mol00924)

• Name: DNA gyrase subunit B (GYRB) ,Escherichia coli
• Synonyms: Type IIA topoisomerase subunit GyrB; acrB; cou; himB; hisU; nalC; parA; pcbA; b3699; JW5625
• Molecule Type: Protein
• Gene Name: gyrB
• Gene ID: 66672403
• Sequence:
  MSNSYDSSSIKVLKGLDAVRKRPGMYIGDTDDGTGLHHMVFEVVDNAIDEALAGHCKEII
  VTIHADNSVSVQDDGRGIPTGIHPEEGVSAAEVIMTVLHAGGKFDDNSYKVSGGLHGVGV
  SVVNALSQKLELVIQREGKIHRQIYEHGVPQAPLAVTGETEKTGTMVRFWPSLETFTNVT
  EFEYEILAKRLRELSFLNSGVSIRLRDKRDGKEDHFHYEGGIKAFVEYLNKNKTPIHPNI
  FYFSTEKDGIGVEVALQWNDGFQENIYCFTNNIPQRDGGTHLAGFRAAMTRTLNAYMDKE
  GYSKKAKVSATGDDAREGLIAVVSVKVPDPKFSSQTKDKLVSSEVKSAVEQQMNELLAEY
  LLENPTDAKIVVGKIIDAARAREAARRAREMTRRKGALDLAGLPGKLADCQERDPALSEL
  YLVEGDSAGGSAKQGRNRKNQAILPLKGKILNVEKARFDKMLSSQEVATLITALGCGIGR
  DEYNPDKLRYHSIIIMTDADVDGSHIRTLLLTFFYRQMPEIVERGHVYIAQPPLYKVKKG
  KQEQYIKDDEAMDQYQISIALDGATLHTNASAPALAGEALEKLVSEYNATQKMINRMERR
  YPKAMLKELIYQPTLTEADLSDEQTVTRWVNALVSELNDKEQHGSQWKFDVHTNAEQNLF
  EPIVRVRTHGVDTDYPLDHEFITGGEYRRICTLGEKLRGLLEEDAFIERGERRQPVASFE
  QALDWLVKESRRGLSIQRYKGLGEMNPEQLWETTMDPESRRMLRVTVKDAIAADQLFTTL
  MGDAVEPRRAFIEENALKAANIDI
• Function: DNA gyrase negatively supercoils closed circular double-stranded DNA in an ATP-dependent manner to maintain chromosomes in an underwound state. This makes better substrates for topoisomerase 4 (ParC and ParE) which is the main enzyme that unlinks newly replicated chromosomes in E.coli. Gyrase catalyzes the interconversion of other topological isomers of double-stranded DNA rings, including catenanes. Relaxes negatively supercoiled DNA in an ATP-independent manner. E.coli gyrase has higher supercoiling activity than other characterized bacterial gyrases; at comparable concentrations E.coli gyrase introduces more supercoils faster than M.tuberculosis gyrase, while M.tuberculosis gyrase has higher decatenation than supercoiling activity compared to E.coli. E.coli makes 15% more negative supercoils in pBR322 plasmid DNA than S.typhimurium; the S.typhimurium GyrB subunit is toxic in E.coli, while the E.coli copy can be expressed in S.typhimurium even though the 2 subunits have 777/804 residues identical. The enzymatic differences between E.coli gyrase and topoisomerase IV are largely due to the GyrA C-terminal domain (approximately residues 524-841) and specifically the GyrA-box.
• Uniprot ID: GYRB_ECOLI

Kingdom: N.A.
Phylum: Proteobacteria
Class: Gammaproteobacteria
Order: Enterobacterales
Family: Enterobacteriaceae
Genus: Escherichia
Species: Escherichia coli

Type(s) of Resistant Mechanism of This Molecule

  ADTT: Aberration of the Drug's Therapeutic Target

  EADR: Epigenetic Alteration of DNA, RNA or Protein

Drug Resistance Data Categorized by Drug

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

Novobiocin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Disease Class: Bacterial infection [1]

• Resistant Disease: Bacterial infection [ICD-11: 1A00-1C4Z]
• Resistant Drug: Novobiocin
• Molecule Alteration: Missense mutation; p.R136C+p.R136H+p.R136S+p.G164V
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Escherichia coli HB101; 634468
• In Vitro Model: Escherichia coli JM109; 562
• In Vitro Model: Escherichia coli strain N4177; 562
• In Vitro Model: Escherichia coli strain CC1; 562
• In Vitro Model: Escherichia coli strain CC5; 562
• In Vitro Model: Escherichia coli strain LE234; 562
• In Vitro Model: Escherichia coli strain LE316; 562
• Experiment for Molecule Alteration: Whole genome sequence assay
• Experiment for Drug Resistance: Broth microdilution method assay
• Mechanism Description: Coumarins are inhibitors of the ATP hydrolysis and DNA supercoiling reactions catalysed by DNA gyrase. four mutations have been identified regaeding conferring coumarin resistance to Escherichia coli: Arg-136 to Cys, His or Ser and Gly-164 to Val.Significant differences in the susceptibility of mutant GyrB proteins to inhibition by either chlorobiocin and novobiocin or coumermycin have been found, suggesting wider contacts between coumermycin and GyrB.

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

Coumermycin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Bacterial infection [1]

• Resistant Disease: Bacterial infection [ICD-11: 1A00-1C4Z]
• Resistant Drug: Coumermycin
• Molecule Alteration: Missense mutation; p.R136C+p.R136H+p.R136S+p.G164V
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Escherichia coli HB101; 634468
• In Vitro Model: Escherichia coli JM109; 562
• In Vitro Model: Escherichia coli strain N4177; 562
• In Vitro Model: Escherichia coli strain CC1; 562
• In Vitro Model: Escherichia coli strain CC5; 562
• In Vitro Model: Escherichia coli strain LE234; 562
• In Vitro Model: Escherichia coli strain LE316; 562
• Experiment for Molecule Alteration: Whole genome sequence assay
• Experiment for Drug Resistance: Broth microdilution method assay
• Mechanism Description: Coumarins are inhibitors of the ATP hydrolysis and DNA supercoiling reactions catalysed by DNA gyrase. four mutations have been identified regaeding conferring coumarin resistance to Escherichia coli: Arg-136 to Cys, His or Ser and Gly-164 to Val.Significant differences in the susceptibility of mutant GyrB proteins to inhibition by either chlorobiocin and novobiocin or coumermycin have been found, suggesting wider contacts between coumermycin and GyrB.

References

• Ref 1: gyrB mutations which confer coumarin resistance also affect DNA supercoiling and ATP hydrolysis by Escherichia coli DNA gyrase. Mol Microbiol. 1992 Jun;6(12):1617-24. doi: 10.1111/j.1365-2958.1992.tb00886.x.