Summary information and primary citation
- PDB-id
-
6z1a;
SNAP-derived features in text and
JSON formats
- Class
- isomerase
- Method
- X-ray (2.3 Å)
- Summary
- Ternary complex of staphylococcus aureus DNA gyrase
with amk12 and DNA
- Reference
-
Kolaric A, Germe T, Hrast M, Stevenson CEM, Lawson DM,
Burton NP, Voros J, Maxwell A, Minovski N, Anderluh M
(2021): "Potent DNA
gyrase inhibitors bind asymmetrically to their target
using symmetrical bifurcated halogen bonds." Nat
Commun, 12, 150. doi: 10.1038/s41467-020-20405-8.
- Abstract
- Novel bacterial type II topoisomerase inhibitors
(NBTIs) stabilize single-strand DNA cleavage breaks by DNA
gyrase but their exact mechanism of action has remained
hypothetical until now. We have designed a small library of
NBTIs with an improved DNA gyrase-binding moiety resulting
in low nanomolar inhibition and very potent antibacterial
activity. They stabilize single-stranded cleavage complexes
and, importantly, we have obtained the crystal structure
where an NBTI binds gyrase-DNA in a single conformation
lacking apparent static disorder. This directly proves the
previously postulated NBTI mechanism of action and shows
that they stabilize single-strand cleavage through
asymmetric intercalation with a shift of the scissile
phosphate. This crystal stucture shows that the chlorine
forms a halogen bond with the backbone carbonyls of the two
symmetry-related Ala68 residues. To the best of our
knowledge, such a so-called symmetrical bifurcated halogen
bond has not been identified in a biological system until
now.
