Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:4.1.99.3 (
PRE
)
1,923
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Conformational sampling of pre- and post-therapy subtype B
HIV-1 protease
sequences derived from a pediatric subject infected via maternal transmission with HIV-1 were characterized by double electron-electron resonance spectroscopy. The conformational ensemble of the
PRE
construct resembles native-like inhibitor bound states. In contrast, the POST construct, which contains accumulated drug-pressure selected mutations, has a predominantly semi-open conformational ensemble, with increased populations of open-like states. The single point mutant L63P, which is contained in
PRE
and POST, has decreased dynamics, particularly in the flap region, and also displays a closed-like conformation of inhibitor-bound states. These findings support our hypothesis that secondary mutations accumulate in
HIV-1 protease
to shift conformational sampling to stabilize open-like conformations, while maintaining the predominant semi-open conformation for activity.
...
PMID:Effects of PRE and POST therapy drug-pressure selected mutations on HIV-1 protease conformational sampling. 2498 95
