M00213
type: Enzyme
rlcp: p361
cath: Heat Shock Protein 90
cath: Ribosomal Protein S5; domain 2
cath: http://ezcatdb.cbrc.jp/EzCatDB/cath/3.40.-.-
cath: http://ezcatdb.cbrc.jp/EzCatDB/cath/-.-.-.-
ec: https://purl.uniprot.org/enzyme/5.99.1.3
uniprot: P0AES6
uniprot: Q9LCX5
kegg enzyme: DNA topoisomerase (ATP-hydrolysing)
kegg enzyme: type II DNA topoisomerase
kegg enzyme: DNA-gyrase
kegg enzyme: deoxyribonucleate topoisomerase
kegg enzyme: deoxyribonucleic topoisomerase
kegg enzyme: topoisomerase
kegg enzyme: DNA topoisomerase II
kegg cofactor: Magnesium
kegg substrate: Double-stranded DNA
kegg substrate: ATP
kegg product: Double-stranded DNA
kegg product: ADP
kegg product: Orthophosphate
pdb: 1ei1A01
pdb: 1ei1B01
pdb: 1aj6A
pdb: 1kznA
pdb: 1kijA01
pdb: 1kijB01
pdb: 1ei1A02
pdb: 1ei1B02
pdb: 1kijA02
pdb: 1kijB02
pdb bound state: Unbound
  compound: Double-stranded DNA
  pdb: 1ei1A01
pdb bound state: Unbound
  compound: Double-stranded DNA
  pdb: 1ei1B01
pdb bound state: Unbound
  compound: Double-stranded DNA
  pdb: 1aj6A
pdb bound state: Unbound
  compound: Double-stranded DNA
  pdb: 1kznA
pdb bound state: Unbound
  compound: Double-stranded DNA
  pdb: 1kijA01
pdb bound state: Unbound
  compound: Double-stranded DNA
  pdb: 1kijB01
pdb bound state: Unbound
  compound: Double-stranded DNA
  pdb: 1ei1A02
pdb bound state: Unbound
  compound: Double-stranded DNA
  pdb: 1ei1B02
pdb bound state: Unbound
  compound: Double-stranded DNA
  pdb: 1kijA02
pdb bound state: Unbound
  compound: Double-stranded DNA
  pdb: 1kijB02
pdb bound state: Analogue
  compound: ATP
  pdb: 1ei1A01
  ligand het code: ANP
pdb bound state: Analogue
  compound: ATP
  pdb: 1ei1B01
  ligand het code: ANP
pdb bound state: Unbound
  compound: ATP
  pdb: 1aj6A
pdb bound state: Unbound
  compound: ATP
  pdb: 1kznA
pdb bound state: Unbound
  compound: ATP
  pdb: 1kijA01
pdb bound state: Unbound
  compound: ATP
  pdb: 1kijB01
pdb bound state: Unbound
  compound: ATP
  pdb: 1ei1A02
pdb bound state: Unbound
  compound: ATP
  pdb: 1ei1B02
pdb bound state: Unbound
  compound: ATP
  pdb: 1kijA02
pdb bound state: Unbound
  compound: ATP
  pdb: 1kijB02
pdb bound state: Unbound
  compound: Magnesium
  pdb: 1ei1A01
pdb bound state: Unbound
  compound: Magnesium
  pdb: 1ei1B01
active site residues resources: Three-dimensional model of Escherichia coli gyrase B subunit crystallized in two-dimensions on novobiocin-linked phospholipid films.
references: Regulation of DNA supercoiling in Escherichia coli: genetic basis of a compensatory mutation in DNA gyrase.
references: Preliminary crystallographic analysis of the ATP-hydrolysing domain of the Escherichia coli DNA gyrase B protein.
references: Crystal structure of an N-terminal fragment of the DNA gyrase B protein.
references: The interaction between coumarin drugs and DNA gyrase.
references: Identifying the catalytic residue of the ATPase reaction of DNA gyrase.
references: Three-dimensional model of Escherichia coli gyrase B subunit crystallized in two-dimensions on novobiocin-linked phospholipid films.
references: A ribosomal protein module in EF-G and DNA gyrase.
references: The nature of inhibition of DNA gyrase by the coumarins and the cyclothialidines revealed by X-ray crystallography.
references: The entropic penalty of ordered water accounts for weaker binding of the antibiotic novobiocin to a resistant mutant of DNA gyrase: a thermodynamic and crystallographic study.
references: The high-resolution crystal structure of a 24-kDa gyrase B fragment from E. coli complexed with one of the most potent coumarin inhibitors, clorobiocin.
references: Identifying Lys359 as a critical residue for the ATP-dependent reactions of Drosophila DNA topoisomerase II.
references: Conformational changes in DNA gyrase revealed by limited proteolysis.
references: Identification of a residue involved in transition-state stabilization in the ATPase reaction of DNA gyrase.
references: Isoleucine 10 is essential for DNA gyrase B function in Escherichia coli.
references: The interaction of DNA gyrase with the bacterial toxin CcdB: evidence for the existence of two gyrase-CcdB complexes.
references: Dimerization of Escherichia coli DNA-gyrase B provides a structural mechanism for activating the ATPase catalytic center.
references: Temperature-sensitive suppressor mutations of the Escherichia coli DNA gyrase B protein.
references: GHKL, an emergent ATPase/kinase superfamily.
references: gyrB-225, a mutation of DNA gyrase that compensates for topoisomerase I deficiency: investigation of its low activity and quinolone hypersensitivity.
references: DNA gyrase interaction with coumarin-based inhibitors: the role of the hydroxybenzoate isopentenyl moiety and the 5'-methyl group of the noviose.
references: An open conformation of the Thermus thermophilus gyrase B ATP-binding domain.
references: Backbone 1H, 13C and 15N resonance assignment of the N-terminal 24 kDa fragment of the gyrase B subunit from E. coli.
references: The role of GyrB in the DNA cleavage-religation reaction of DNA gyrase: a proposed two metal-ion mechanism.
references: Active-site residues of Escherichia coli DNA gyrase required in coupling ATP hydrolysis to DNA supercoiling and amino acid substitutions leading to novobiocin resistance.
comment: This protein is B subunit of DNA-gyrase, which catalyzes ATP hydrolysis. The A subunit of this enzyme catalyzes DNA brekage and religation (see M00137). PDB structure, 1ei1, corresponds to the N-terminal half of the B subunit of DNA-gyrase. The other region, C-terminal half of the B subunit is responsible for the interaction with DNA and the A subunit, according to the literature [19]. According to the literature [13] & [18], the reaction proceeds as follows; (1) Glu42 (of 1ei1) acts as a general base, to activate a water molecule, which must be in-line for a nucleophilic attack on the gamma-phosphate of ATP. Lys337 may stabilize the activated water during this reaction. (2) Lys337 stabilizes the transition-state, along with mainchain amide of resdiues 115-119. Magnesium ion, possibly bound to Asn46, stabilizes the transition-state.

Heat Shock Protein 90
type: Cath
references: http://www.cathdb.info/version/latest/superfamily/3.30.565.10
catalytic domain: index.html

Ribosomal Protein S5; domain 2
type: Cath
references: http://www.cathdb.info/version/latest/superfamily/3.30.230.10
catalytic domain: index.html

Magnesium
type: KeggCofactor
references: KEGG:C00305
compound type: divalent metal (Ca2+, Mg2+)
references: CHEBI:18420
references: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi

Double-stranded DNA
type: KeggSubstrate
references: KEGG:C00434
compound type: nucleic acids
type: KeggProduct

ATP
type: KeggSubstrate
references: KEGG:C00002
compound type: amine group
compound type: nucleotide
references: CHEBI:15422
references: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi

ADP
type: KeggProduct
references: KEGG:C00008
compound type: amine group
compound type: nucleotide
references: CHEBI:16761
references: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi

Orthophosphate
type: KeggProduct
references: KEGG:C00009
compound type: phosphate group/phosphate ion
references: CHEBI:26078
references: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi

1ei1A01
type: Pdb
references: 1ei1
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1ei1
catalytic residue: GLU 42
cofactor binding residue: ASN 46(magnesium binding)
main chain in catalysis: LEU 115;HIS 116;GLY 117;VAL 118;GLY 119

1ei1B01
type: Pdb
references: 1ei1
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1ei1
catalytic residue: GLU 442
cofactor binding residue: ASN 446(magnesium binding)
main chain in catalysis: LEU 515;HIS 516;GLY 517;VAL 518;GLY 519

1aj6A
type: Pdb
references: 1aj6
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1aj6
catalytic residue: GLU 42
cofactor binding residue: ASN 46(magnesium binding)
main chain in catalysis: LEU 115;HIS 116;GLY 117;VAL 118;GLY 119

1kznA
type: Pdb
references: 1kzn
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1kzn
catalytic residue: GLU 42
cofactor binding residue: ASN 46(magnesium binding)
main chain in catalysis: ;HIS 116;GLY 117;VAL 118;GLY 119
comment: invisible 97-115

1kijA01
type: Pdb
references: 1kij
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1kij
catalytic residue: GLU 41
cofactor binding residue: ASN 45(magnesium binding)
main chain in catalysis: LEU 114;HIS 115;GLY 116;VAL 117;GLY 118

1kijB01
type: Pdb
references: 1kij
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1kij
catalytic residue: GLU 41
cofactor binding residue: ASN 45(magnesium binding)
main chain in catalysis: LEU 114;HIS 115;GLY 116;VAL 117;GLY 118

1ei1A02
type: Pdb
references: 1ei1
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1ei1
catalytic residue: LYS 337

1ei1B02
type: Pdb
references: 1ei1
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1ei1
catalytic residue: LYS 737

1kijA02
type: Pdb
references: 1kij
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1kij
catalytic residue: LYS 337

1kijB02
type: Pdb
references: 1kij
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1kij
catalytic residue: LYS 337

Regulation of DNA supercoiling in Escherichia coli: genetic basis of a compensatory mutation in DNA gyrase.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/2547660
journal: FEBS Lett
volume: 253
pages: 67-70
published year: 1989
authors:
  item: McEachern F
  item: Fisher LM

Preliminary crystallographic analysis of the ATP-hydrolysing domain of the Escherichia coli DNA gyrase B protein.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/1846427
journal: J Mol Biol
volume: 217
pages: 15-7
published year: 1991
authors:
  item: Jackson AP
  item: Maxwell A
  item: Wigley DB

Crystal structure of an N-terminal fragment of the DNA gyrase B protein.
type: BibliographicResource
comment: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 1-392
medline id: 91270367
references: http://www.ncbi.nlm.nih.gov/pubmed/1646964
journal: Nature
volume: 351
pages: 624-9
published year: 1991
authors:
  item: Wigley DB
  item: Davies GJ
  item: Dodson EJ
  item: Maxwell A
  item: Dodson G
references: P0AES6

The interaction between coumarin drugs and DNA gyrase.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/8231802
journal: Mol Microbiol
volume: 9
pages: 681-6
published year: 1993
authors:
  item: Maxwell A

Identifying the catalytic residue of the ATPase reaction of DNA gyrase.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/8248233
journal: Proc Natl Acad Sci U S A
volume: 90
pages: 11232-6
published year: 1993
authors:
  item: Jackson AP
  item: Maxwell A

Three-dimensional model of Escherichia coli gyrase B subunit crystallized in two-dimensions on novobiocin-linked phospholipid films.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/8107146
journal: J Mol Biol
volume: 236
pages: 618-28
published year: 1994
authors:
  item: Celia H
  item: Hoermann L
  item: Schultz P
  item: Lebeau L
  item: Mallouh V
  item: Wigley DB
  item: Wang JC
  item: Mioskowski C
  item: Oudet P

A ribosomal protein module in EF-G and DNA gyrase.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/7719848
journal: Nat Struct Biol
volume: 2
pages: 25-6
published year: 1995
authors:
  item: Murzin AG

The nature of inhibition of DNA gyrase by the coumarins and the cyclothialidines revealed by X-ray crystallography.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/8635474
journal: EMBO J
volume: 15
pages: 1412-20
published year: 1996
authors:
  item: Lewis RJ
  item: Singh OM
  item: Smith CV
  item: Skarzynski T
  item: Maxwell A
  item: Wonacott AJ
  item: Wigley DB

The entropic penalty of ordered water accounts for weaker binding of the antibiotic novobiocin to a resistant mutant of DNA gyrase: a thermodynamic and crystallographic study.
type: BibliographicResource
comment: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 1-220 OF MUTANT HIS-135
medline id: 97392632
references: http://www.ncbi.nlm.nih.gov/pubmed/9245398
journal: Biochemistry
volume: 36
pages: 9663-73
published year: 1997
authors:
  item: Holdgate GA
  item: Tunnicliffe A
  item: Ward WH
  item: Weston SA
  item: Rosenbrock G
  item: Barth PT
  item: Taylor IW
  item: Pauptit RA
  item: Timms D
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: P0AES6

The high-resolution crystal structure of a 24-kDa gyrase B fragment from E. coli complexed with one of the most potent coumarin inhibitors, clorobiocin.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/9144789
journal: Proteins
volume: 28
pages: 41-52
published year: 1997
authors:
  item: Tsai FT
  item: Singh OM
  item: Skarzynski T
  item: Wonacott AJ
  item: Weston S
  item: Tucker A
  item: Pauptit RA
  item: Breeze AL
  item: Poyser JP
  item: O'Brien R
  item: Ladbury JE
  item: Wigley DB

Identifying Lys359 as a critical residue for the ATP-dependent reactions of Drosophila DNA topoisomerase II.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/9545289
journal: J Biol Chem
volume: 273
pages: 9586-92
published year: 1998
authors:
  item: Hu T
  item: Chang S
  item: Hsieh T

Conformational changes in DNA gyrase revealed by limited proteolysis.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/9712889
journal: J Biol Chem
volume: 273
pages: 22606-14
published year: 1998
authors:
  item: Kampranis SC
  item: Maxwell A

Identification of a residue involved in transition-state stabilization in the ATPase reaction of DNA gyrase.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/9657678
journal: Biochemistry
volume: 37
pages: 9658-67
published year: 1998
authors:
  item: Smith CV
  item: Maxwell A

Isoleucine 10 is essential for DNA gyrase B function in Escherichia coli.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/10575351
journal: Biochimie
volume: 81
pages: 973-80
published year: 1999
authors:
  item: Brino L
  item: Bronner C
  item: Oudet P
  item: Mousli M

The interaction of DNA gyrase with the bacterial toxin CcdB: evidence for the existence of two gyrase-CcdB complexes.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/10543963
journal: J Mol Biol
volume: 293
pages: 733-44
published year: 1999
authors:
  item: Kampranis SC
  item: Howells AJ
  item: Maxwell A

Dimerization of Escherichia coli DNA-gyrase B provides a structural mechanism for activating the ATPase catalytic center.
type: BibliographicResource
comment: X-ray crystallography
references: http://www.ncbi.nlm.nih.gov/pubmed/10734094
journal: J Biol Chem
volume: 275
pages: 9468-75
published year: 2000
authors:
  item: Brino L
  item: Urzhumtsev A
  item: Mousli M
  item: Bronner C
  item: Mitschler A
  item: Oudet P
  item: Moras D
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl

Temperature-sensitive suppressor mutations of the Escherichia coli DNA gyrase B protein.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/10850814
journal: Protein Sci
volume: 9
pages: 1035-7
published year: 2000
authors:
  item: Blance SJ
  item: Williams NL
  item: Preston ZA
  item: Bishara J
  item: Smyth MS
  item: Maxwell A

GHKL, an emergent ATPase/kinase superfamily.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/10637609
journal: Trends Biochem Sci
volume: 25
pages: 24-8
published year: 2000
authors:
  item: Dutta R
  item: Inouye M

gyrB-225, a mutation of DNA gyrase that compensates for topoisomerase I deficiency: investigation of its low activity and quinolone hypersensitivity.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/11399091
journal: J Mol Biol
volume: 309
pages: 1219-31
published year: 2001
authors:
  item: Heddle JG
  item: Lu T
  item: Zhao X
  item: Drlica K
  item: Maxwell A

DNA gyrase interaction with coumarin-based inhibitors: the role of the hydroxybenzoate isopentenyl moiety and the 5'-methyl group of the noviose.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/12044152
journal: Biochemistry
volume: 41
pages: 7217-23
published year: 2002
authors:
  item: Lafitte D
  item: Lamour V
  item: Tsvetkov PO
  item: Makarov AA
  item: Klich M
  item: Deprez P
  item: Moras D
  item: Briand C
  item: Gilli R
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl

An open conformation of the Thermus thermophilus gyrase B ATP-binding domain.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/11850422
journal: J Biol Chem
volume: 277
pages: 18947-53
published year: 2002
authors:
  item: Lamour V
  item: Hoermann L
  item: Jeltsch JM
  item: Oudet P
  item: Moras D
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl

Backbone 1H, 13C and 15N resonance assignment of the N-terminal 24 kDa fragment of the gyrase B subunit from E. coli.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/12018484
journal: J Biomol NMR
volume: 22
pages: 369-70
published year: 2002
authors:
  item: Bellanda M
  item: Peggion E
  item: Otting G
  item: Weigelt J
  item: Perdona E
  item: Domenici E
  item: Marchioro C
  item: Mammi S

The role of GyrB in the DNA cleavage-religation reaction of DNA gyrase: a proposed two metal-ion mechanism.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/12051843
journal: J Mol Biol
volume: 318
pages: 361-71
published year: 2002
authors:
  item: Noble CG
  item: Maxwell A

Active-site residues of Escherichia coli DNA gyrase required in coupling ATP hydrolysis to DNA supercoiling and amino acid substitutions leading to novobiocin resistance.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/12604539
journal: Antimicrob Agents Chemother
volume: 47
pages: 1037-46
published year: 2003
authors:
  item: Gross CH
  item: Parsons JD
  item: Grossman TH
  item: Charifson PS
  item: Bellon S
  item: Jernee J
  item: Dwyer M
  item: Chambers SP
  item: Markland W
  item: Botfield M
  item: Raybuck SA

ReferenceForCatalyticMechanism
reference index: 3
reference section: p.627-629

ReferenceForCatalyticMechanism
reference index: 5
reference section: Fig.1B
reference step: 1

ReferenceForCatalyticMechanism
reference index: 16
reference section: p.9472-9473

ReferenceForCatalyticMechanism
reference index: 18
reference section: p.27

ReferenceForCatalyticMechanism
reference index: 21
reference section: Fig.6
reference step: 3