Aminopeptidase

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^[1].
Deblocking aminopeptidase (DAP) is an exoprotease aminopeptidase which can release N-terminal amino acids from blocked peptides^[2].
Beta-peptidyl AP (BapA) cleaves N-terminal β-homoamino acid from peptides of length 2 to 6.^[3]
.
M1 family AP are Zn+2 containing amino peptidases^[4]

Aminopeptidases catalyze a release of an N-terminal amino acid from a peptide, amide, or arylamide.

Aminopeptidase from Aeromonas proteolytica^[5]

The selective inhibition of an , a hydrolase, by 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. (1.3 Å resolution) as well as fluorescence titrations of these drugs with AAP confirmed that , in which the in the active site of AAP and the (PDB code: 3vh9). 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 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

Bacterial leucine aminopeptidase complex with 8-hydroxyquinoline, glycerol, SCN, Zn+2 (magenta), Na+ (cyan) and Cl- (green) ions (PDB code 3vh9)

Drag the structure with the mouse to rotate

Additional ResourcesAdditional Resources

For additional information, see:
Amino Acid Synthesis & Metabolism
Streptomyces griseus Aminopeptidase (SGAP)

ReferencesReferences

↑ Basten DE, Dekker PJ, Schaap PJ. Aminopeptidase C of Aspergillus niger is a novel phenylalanine aminopeptidase. Appl Environ Microbiol. 2003 Feb;69(2):1246-50. PMID:12571053 doi:10.1128/AEM.69.2.1246-1250.2003
↑ Jia B, Lee S, Pham BP, Kwack JM, Jin H, Li J, Wang Y, Cheong GW. Biochemical characterization of deblocking aminopeptidases from the hyperthermophilic archaeon Thermococcus kodakarensis KOD1. Biosci Biotechnol Biochem. 2011;75(6):1160-6. PMID:21670507 doi:10.1271/bbb.110114
↑ Taylor A. Aminopeptidases: structure and function. FASEB J. 1993 Feb 1;7(2):290-8. PMID:8440407
↑ Cadel S, Darmon C, Pernier J, Hervé G, Foulon T. The M1 family of vertebrate aminopeptidases: role of evolutionarily conserved tyrosines in the enzymatic mechanism of aminopeptidase B. Biochimie. 2015 Feb;109:67-77. PMID:25530263 doi:10.1016/j.biochi.2014.12.009
↑ Hanaya K, Suetsugu M, Saijo S, Yamato I, Aoki S. 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. J Biol Inorg Chem. 2012 Feb 5. PMID:22311113 doi:10.1007/s00775-012-0873-4

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Eran Hodis, David Canner, Alexander Berchansky, Michal Harel, Joel L. Sussman

[1] Basten DE, Dekker PJ, Schaap PJ. Aminopeptidase C of Aspergillus niger is a novel phenylalanine aminopeptidase. Appl Environ Microbiol. 2003 Feb;69(2):1246-50. PMID:12571053 doi:10.1128/AEM.69.2.1246-1250.2003

[2] Jia B, Lee S, Pham BP, Kwack JM, Jin H, Li J, Wang Y, Cheong GW. Biochemical characterization of deblocking aminopeptidases from the hyperthermophilic archaeon Thermococcus kodakarensis KOD1. Biosci Biotechnol Biochem. 2011;75(6):1160-6. PMID:21670507 doi:10.1271/bbb.110114

[3] Taylor A. Aminopeptidases: structure and function. FASEB J. 1993 Feb 1;7(2):290-8. PMID:8440407

[4] Cadel S, Darmon C, Pernier J, Hervé G, Foulon T. The M1 family of vertebrate aminopeptidases: role of evolutionarily conserved tyrosines in the enzymatic mechanism of aminopeptidase B. Biochimie. 2015 Feb;109:67-77. PMID:25530263 doi:10.1016/j.biochi.2014.12.009

[5] Hanaya K, Suetsugu M, Saijo S, Yamato I, Aoki S. 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. J Biol Inorg Chem. 2012 Feb 5. PMID:22311113 doi:10.1007/s00775-012-0873-4

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