3vh9: Difference between revisions

<StructureSection load='3vh9' size='340' side='right'caption='[[3vh9]], [[Resolution|resolution]] 1.29&Aring;' scene=''>

<table><tr><td colspan='2'>[[3vh9]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Vibrio_proteolyticus Vibrio proteolyticus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3VH9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3VH9 FirstGlance]. <br>

</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.29&#8491;</td></tr>

<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=HQY:QUINOLIN-8-OL'>HQY</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=SCN:THIOCYANATE+ION'>SCN</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>

<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3vh9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3vh9 OCA], [https://pdbe.org/3vh9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3vh9 RCSB], [https://www.ebi.ac.uk/pdbsum/3vh9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3vh9 ProSAT]</span></td></tr>

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The selective inhibition of an aminopeptidase from Aeromonas proteolytica (AAP), a dinuclear Zn(2+) hydrolase, by 8-quinolinol (8-hydroxyquinoline, 8-HQ) derivatives is reported. We previously reported on the preparation of 8-HQ-pendant cyclens as Zn(2+) fluorophores (cyclen is 1,4,7,10-tetraazacyclododecane), in which the nitrogen and phenolate of the 8-HQ units (as well as the four nitrogens of cyclen) bind to Zn(2+) in a bidentate manner to form very stable Zn(2+) complexes at neutral pH (K (d) = 8-50 fM at pH 7.4). On the basis of this finding, it was hypothesized that 8-HQ derivatives have the potential to function as specific inhibitors of Zn(2+) enzymes, especially dinuclear Zn(2+) hydrolases. Assays of 8-HQ derivatives as inhibitors were performed against commercially available dinuclear Zn(2+) enzymes such as AAP and alkaline phosphatase. 8-HQ and the 5-substituted 8-HQ derivatives were found to be competitive inhibitors of AAP with inhibition constants of 0.16-29 muM at pH 8.0. The nitrogen at the 1-position and the hydroxide at the 8-position of 8-HQ were found to be essential for the inhibition of AAP. Fluorescence titrations of these drugs with AAP and an X-ray crystal structure analysis of an AAP-8-HQ complex (1.3-A resolution) confirmed that 8-HQ binds to AAP in the "Pyr-out" mode, in which the hydroxide anion of 8-HQ bridges two Zn(2+) ions (Zn1 and Zn2) in the active site of AAP and the nitrogen atom of 8-HQ coordinates to Zn1 (Protein Data Bank code 3VH9).

Potent inhibition of dinuclear zinc(II) peptidase, an aminopeptidase from Aeromonas proteolytica, by 8-quinolinol derivatives: inhibitor design based on Zn(2+) fluorophores, kinetic, and X-ray crystallographic study.,Hanaya K, Suetsugu M, Saijo S, Yamato I, Aoki S J Biol Inorg Chem. 2012 Feb 5. PMID:22311113<ref>PMID:22311113</ref>

==See Also==

*[[Aminopeptidase|Aminopeptidase]]

*[[Aminopeptidase 3D structures|Aminopeptidase 3D structures]]

== References ==

<references/>

</StructureSection>

[[Category: Large Structures]]

[[Category: Aoki S]]

[[Category: Hanaya K]]

[[Category: Kobayashi K]]

[[Category: Saijo S]]

[[Category: Suetsugu M]]

[[Category: Yamato I]]