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PDBsum entry 5cty
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Isomerase/isomerase inhibitor
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PDB id
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5cty
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PDB id:
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| Name: |
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Isomerase/isomerase inhibitor
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Title:
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Crystal structure of the atp binding domain of s. Aureus gyrb complexed with a fragment
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Structure:
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DNA gyrase subunit b. Chain: a, b. Fragment: atp binding domain, unp residues 2-234 (delta 105-127). Engineered: yes
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Source:
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Staphylococcus aureus. Organism_taxid: 1280. Gene: gyrb. Expressed in: escherichia coli. Expression_system_taxid: 469008.
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Resolution:
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1.60Å
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R-factor:
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0.173
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R-free:
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0.201
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Authors:
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O.A.Andersen,J.Barker,R.K.Cheng,J.Kahmann,B.Felicetti,M.Wood, C.Scheich,M.Mesleh,J.B.Cross,J.Zhang,Q.Yang,B.Lippa,M.D.Ryan
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Key ref:
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M.F.Mesleh
et al.
(2016).
Fragment-based discovery of DNA gyrase inhibitors targeting the ATPase subunit of GyrB.
Bioorg Med Chem Lett,
26,
1314-1318.
PubMed id:
DOI:
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Date:
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24-Jul-15
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Release date:
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03-Feb-16
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PROCHECK
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Headers
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References
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P0A0K8
(GYRB_STAAU) -
DNA gyrase subunit B from Staphylococcus aureus
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Seq:
Struc:
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644 a.a.
192 a.a.
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Key: |
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Secondary structure |
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CATH domain |
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Enzyme class:
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E.C.5.6.2.2
- Dna topoisomerase (ATP-hydrolyzing).
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DOI no:
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Bioorg Med Chem Lett
26:1314-1318
(2016)
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PubMed id:
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Fragment-based discovery of DNA gyrase inhibitors targeting the ATPase subunit of GyrB.
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M.F.Mesleh,
J.B.Cross,
J.Zhang,
J.Kahmann,
O.A.Andersen,
J.Barker,
R.K.Cheng,
B.Felicetti,
M.Wood,
A.T.Hadfield,
C.Scheich,
T.I.Moy,
Q.Yang,
J.Shotwell,
K.Nguyen,
B.Lippa,
R.Dolle,
M.D.Ryan.
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ABSTRACT
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Inhibitors of the ATPase function of bacterial DNA gyrase, located in the GyrB
subunit and its related ParE subunit in topoisomerase IV, have demonstrated
antibacterial activity. In this study we describe an NMR fragment-based
screening effort targeting Staphylococcus aureus GyrB that identified several
attractive and novel starting points with good ligand efficiency. Fragment hits
were further characterized using NMR binding studies against full-length S.
aureus GyrB and Escherichia coli ParE. X-ray co-crystal structures of select
fragment hits confirmed binding and suggested a path for medicinal chemistry
optimization. The identification, characterization, and elaboration of one of
these fragment series to a 0.265μM inhibitor is described herein.
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