Aminopeptidase

spinqualitylabelsall models Bacterial leucine aminopeptidase complex with 8-hydroxyquinoline, glycerol, SCN, Zn+2 (magenta), Na+ (cyan) and Cl- (green) ions (PDB code 3vh9) Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Function Aminopeptidases (AP) (EC 3) are metal - mostly Zn-dependent enzymes involved in the digestion of proteins. Cytosol AP (Cyt-AP) and AP N (APN) remove N-terminal amino acids. The AP are classified by the amino acid which they hydrolyze. Other types of AP are: Cold-activated AP (Col-AP) Heat stable AP from Thermus thermophilus (AmpT) AP from Staphylococcus aureus (AmpS) SGAP from Stereomyces griseus. See details in Streptomyces griseus Aminopeptidase (SGAP). Alanine aminopeptidase is called aminopeptidase N. See details in Aminopeptidase N. Aminopeptidase C is a Phe aminopeptidase from Aspergillus niger. Deblocking aminopeptidase (DAP) is an exoprotease aminopeptidase which can release N-terminal amino acids from blocked peptides. Beta-peptidyl AP (BapA) cleaves N-terminal β-homoamino acid from peptides of length 2 to 6. . M1 family AP are Zn+2 containing amino peptidases Aminopeptidases catalyze a release of an N-terminal amino acid from a peptide, amide, or arylamide. Aminopeptidase from Aeromonas proteolytica 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 with 8-HQ complex (1.3 Å resolution) as well as fluorescence titrations of these drugs with AAP confirmed that 8-hydroxyquinoline 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). Overlap of active site of free AAP (colored green) containing Zn2+-bound water molecule (H2O or OH-; red sphere) (1rtq) bridging two Zn2+ and AAP–8-HQ complex (darkmagenta, 3vh9). Two Zn2+ are depicted as magenta spheres. S. griseus aminopeptidase S. griseus aminopeptidase (SGAP) cleaves the N-terminal amino acid from a peptide or protein, and is specific for larger hydrophobic acids, especially leucine. No cleavage occurs if the next residue is proline. The active site of the enzyme contains two Zn2+ ions with His85 and Asp160 as ligands for one ion, and Glu132 and His247 as ligands for the second ion. Asp97 is a common ligand to both ions. What appears to be a phosphate anion is bound to both zinc atoms, replacing the water molecule/hydroxide ion normally found in this class of enzyme. See details of SGAP in Streptomyces griseus Aminopeptidase (SGAP). 3D Structures of Aminopeptidase Aminopeptidase 3D structures

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EC
Streptomyces griseus Aminopeptidase (SGAP)

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