Moses Prabu-Jeyabalan

TL;DR: The crystal structures of complexes of an inactive variant of HIV-1 protease with six peptides that correspond to the natural substrate cleavage sites are solved, revealing an asymmetric shape rather than a particular amino acid sequence in this enzyme.

TL;DR: Modification of the substitution pattern on the phenylsulfonamide P2' substituent of TMC126 created an interesting SAR, with the close analogue TMC114 being found to have a similar antiviral activity against the mutant and the wild-type viruses.

TL;DR: TMC114's potency against MDR viruses is likely a combination of its extremely high affinity and close fit within the substrate envelope, a property that may be associated with decreased susceptibility to drug-resistant mutations relative to that of first-generation inhibitors.

TL;DR: Interdependence of the conformational changes allows the protease to exhibit its wide range of substrate specificity.

TL;DR: This study examines the impact of drug-resistant mutations in HIV-1 protease on substrate recognition and demonstrates that most primary active site mutations do not extensively contact substrates, but are critical to inhibitor binding.