3vh9

Crystal structure of Aeromonas proteolytica aminopeptidase complexed with 8-quinolinol

spinqualitylabelsall models 3vh9, resolution 1.29Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3vh9 is a 1 chain structure with sequence from Vibrio proteolyticus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: CL, GOL, HQY, NA, SCN, ZN Related: 1lok, 1rtq, 1amp, 1cp6, 1txr, 1xry, 2iq6, 1igb, 1ft7, 2prq, 2nyq, 2anp, 3b35, 3b3t, 3b3s, 3b3v, 3b3c, 3b7i, 3b3w, 3fh4, 2dea Activity: Bacterial leucyl aminopeptidase, with EC number 3.4.11.10 Resources: FirstGlance, OCA, RCSB, PDBsum Publication Abstract from PubMed 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Aminopeptidase Journal:JBIC:15

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