This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.
Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.
Journal:JBIC:15
From Proteopedia
| Line 4: | Line 4: | ||
<hr/> | <hr/> | ||
<b>Molecular Tour</b><br> | <b>Molecular Tour</b><br> | ||
| - | + | The selective inhibition of an aminopeptidase from Aeromonas proteolytica (AAP), a dinuclear Zn2+ hydrolase, by 8-quinolinol (8-hydroxyquinoline, 8-HQ) derivatives is reported. Based on our findings about 8-HQ-based Zn2+ fluorophores, it was hypothesized that 8-HQ derivatives have the potential to function as specific inhibitors of Zn2+ enzymes, especially dinuclear Zn2+ hydrolases. Inhibitory assays of 8-HQ derivatives against AAP disclosed that the 8-HQ and 5-substituted 8-HQ′s are competitive inhibitors for AAP with inhibition constants (Ki) of 0.16—29 μM at pH 8.0. X-ray crystal structure analysis of an AAP–8-HQ complex (1.3 ֵ resolution) as well as fluorescence titrations of these drugs with AAP confirmed that 8-HQ binds to AAP in the “Pyr-out” mode, in which the hydroxide anion of 8-HQ bridges two Zn2+ (Zn1 and Zn2) in the active site of AAP and the nitrogen atom of 8-HQ coordinates to Zn1 (PDB code: [[3vh9]]). | |
Revision as of 10:09, 5 January 2012
|
Potent Inhibition of Dinuclear Zinc(II) Peptidase, an Aminopeptidase from Aeromonas proteolytica, by 8-Quinolinol Derivatives: Inhibitor Design Based on Zn2+ Fluorophores, Kinetic, and X-ray Crystallographic Study
Shin Aoki[1]
Molecular Tour
The selective inhibition of an aminopeptidase from Aeromonas proteolytica (AAP), a dinuclear Zn2+ hydrolase, by 8-quinolinol (8-hydroxyquinoline, 8-HQ) derivatives is reported. Based on our findings about 8-HQ-based Zn2+ fluorophores, it was hypothesized that 8-HQ derivatives have the potential to function as specific inhibitors of Zn2+ enzymes, especially dinuclear Zn2+ hydrolases. Inhibitory assays of 8-HQ derivatives against AAP disclosed that the 8-HQ and 5-substituted 8-HQ′s are competitive inhibitors for AAP with inhibition constants (Ki) of 0.16—29 μM at pH 8.0. X-ray crystal structure analysis of an AAP–8-HQ complex (1.3 ֵ resolution) as well as fluorescence titrations of these drugs with AAP confirmed that 8-HQ binds to AAP in the “Pyr-out” mode, in which the hydroxide anion of 8-HQ bridges two Zn2+ (Zn1 and Zn2) in the active site of AAP and the nitrogen atom of 8-HQ coordinates to Zn1 (PDB code: 3vh9).
- ↑ no reference yet
