Journal:JBIC:15

The selective inhibition of an <scene name='Journal:JBIC:15/Cv/2'>aminopeptidase from Aeromonas proteolytica (AAP)</scene>, a <scene name='Journal:JBIC:15/Cv/3'>dinuclear Zn2+</scene> hydrolase, by <scene name='Journal:JBIC:15/Cv/10'>8-quinolinol (8-hydroxyquinoline, 8-HQ)</scene> 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&#8242;s are competitive inhibitors for AAP with inhibition constants (''K''i) of 0.16—29 &#956;M at pH 8.0. <scene name='Journal:JBIC:15/Cv/11'>X-ray crystal structure analysis of an AAP with 8-HQ complex</scene> (1.3 Å resolution) as well as fluorescence titrations of these drugs with AAP confirmed that <scene name='Journal:JBIC:15/Cv/13'>8-hydroxyquinoline binds to AAP in the 'Pyr-out' mode</scene>, in which the <scene name='Journal:JBIC:15/Cv/15'>hydroxide anion of 8-HQ bridges two Zn2+ (Zn1 and Zn2)</scene> in the active site of AAP and the <scene name='Journal:JBIC:15/Cv/17'>nitrogen atom of 8-HQ coordinates to Zn1</scene> (PDB code: [[3vh9]]). <scene name='Journal:JBIC:15/Cv/18'>Overlap of active site</scene> of <span style="color:lime;background-color:black;font-weight:bold;">free AAP (colored green)</span> containing Zn²⁺-bound <font color='red'><b>water molecule (H2O or OH-; red sphere)</b></font> ([[1rtq]]) bridging two Zn²⁺ and <font color='darkmagenta'><b>AAP–8-HQ complex (darkmagenta,</b></font> [[3vh9]]). <font color='magenta'><b>Two Zn²⁺ are depicted as magenta spheres</b></font>.

The selective inhibition of an <scene name='Journal:JBIC:15/Cv/2'>aminopeptidase from Aeromonas proteolytica (AAP)</scene>, a <scene name='Journal:JBIC:15/Cv/3'>dinuclear Zn2+</scene> hydrolase, by <scene name='Journal:JBIC:15/Cv/10'>8-quinolinol (8-hydroxyquinoline, 8-HQ)</scene> 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&#8242;s are competitive inhibitors for AAP with inhibition constants (''K''i) of 0.16—29 &#956;M at pH 8.0. <scene name='Journal:JBIC:15/Cv/11'>X-ray crystal structure analysis of an AAP with 8-HQ complex</scene> (1.3 Å resolution) as well as fluorescence titrations of these drugs with AAP confirmed that <scene name='Journal:JBIC:15/Cv/13'>8-hydroxyquinoline binds to AAP in the 'Pyr-out' mode</scene>, in which the <scene name='Journal:JBIC:15/Cv/15'>hydroxide anion of 8-HQ bridges two Zn2+ (Zn1 and Zn2)</scene> in the active site of AAP and the <scene name='Journal:JBIC:15/Cv/17'>nitrogen atom of 8-HQ coordinates to Zn1</scene> (PDB code: [[3vh9]]). <scene name='Journal:JBIC:15/Cv/18'>Overlap of active site</scene> of <span style="color:lime;background-color:black;font-weight:bold;">free AAP (colored green)</span> containing Zn²⁺-bound <font color='red'><b>water molecule (H2O or OH-; red sphere)</b></font> ([[1rtq]]) bridging two Zn²⁺ and <font color='darkmagenta'><b>AAP–8-HQ complex (darkmagenta,</b></font> [[3vh9]]). <font color='magenta'><b>Two Zn²⁺ are depicted as magenta spheres</b></font>.

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