Pyridomycin bridges the NADH- and substrate-binding pockets of the enoyl reductase InhA.
Nat Chem Biol
; 10(2): 96-8, 2014 Feb.
Article
in En
| MEDLINE
| ID: mdl-24292073
ABSTRACT
Pyridomycin, a natural product with potent antituberculosis activity, inhibits a major drug target, the InhA enoyl reductase. Here, we unveil the co-crystal structure and unique ability of pyridomycin to block both the NADH cofactor- and lipid substrate-binding pockets of InhA. This is to our knowledge a first-of-a-kind binding mode that discloses a new means of InhA inhibition. Proof-of-principle studies show how structure-assisted drug design can improve the activity of new pyridomycin derivatives.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Oligopeptides
/
Oxidoreductases
/
Bacterial Proteins
/
NAD
/
Antitubercular Agents
Language:
En
Journal:
Nat Chem Biol
Journal subject:
BIOLOGIA
/
QUIMICA
Year:
2014
Document type:
Article
Affiliation country:
Switzerland