Aminopeptidase

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<StructureSection load='VH9.pdb' size='450' side='right' scene='Journal:JBIC:15/Cv/1' caption='Bacterial leucine aminopeptidase complex with 8-hydroxyquinoline, glycerol, SCN, Zn+2 (magenta), Na+ (cyan) and Cl- (green) ions (PDB code [[3vh9]])'>[[Aminopeptidase|Aminopeptidases]] (AP) ([[EC]] 3) are metal - mostly Zn-dependent enzymes involved in the digestion of proteins. Cytosol AP (Cyt-AP), deblocking AP (DAP) 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) and SGAP from ''Stereomyces griseus''. Aminopeptidases catalyze a release of an N-terminal amino acid from a peptide, amide, or arylamide. See details of SGAP in [[Streptomyces griseus Aminopeptidase (SGAP)]]. Beta-peptidyl AP (BapA) cleaves N-terminal β-homoamino acid from peptides of length 2 to 6.
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<StructureSection load='' size='350' side='right' scene='Journal:JBIC:15/Cv/1' caption='Bacterial leucine aminopeptidase complex with 8-hydroxyquinoline, glycerol, SCN, Zn+2 (magenta), Na+ (cyan) and Cl- (green) ions (PDB code [[3vh9]])'>
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__TOC__
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== Function ==
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[[Aminopeptidase|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:<br />
 +
* '''Cold-activated AP''' (Col-AP)<br />
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* '''Heat stable AP''' from ''Thermus thermophilus'' (AmpT)<br />
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* '''AP from ''Staphylococcus aureus''''' (AmpS)<br />
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* '''SGAP''' from ''Stereomyces griseus''. See details in [[Streptomyces griseus Aminopeptidase (SGAP)]].<br />
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* '''Alanine aminopeptidase''' is called '''aminopeptidase N'''. See details in [[Aminopeptidase N]].<br />
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* '''Aminopeptidase C''' is a Phe aminopeptidase from ''Aspergillus niger''<ref>PMID:12571053</ref>.<br />
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* '''Deblocking aminopeptidase''' (DAP) is an exoprotease aminopeptidase which can release N-terminal amino acids from blocked peptides<ref>PMID:21670507</ref>.<br />
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* '''Beta-peptidyl AP''' (BapA) cleaves N-terminal β-homoamino acid from peptides of length 2 to 6.<ref>PMID:8440407</ref><br />.
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* '''M1 family AP''' are Zn+2 containing amino peptidases<ref>PMID:25530263</ref><br />
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Aminopeptidases catalyze a release of an N-terminal amino acid from a peptide, amide, or arylamide.
== Aminopeptidase from ''Aeromonas proteolytica''<ref>DOI 10.1007/s00775-012-0873-4</ref> ==
== Aminopeptidase from ''Aeromonas proteolytica''<ref>DOI 10.1007/s00775-012-0873-4</ref> ==
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The <scene name='Aminopeptidase/Active_site/1'>active site</scene> 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)]].
The <scene name='Aminopeptidase/Active_site/1'>active site</scene> 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)]].
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</StructureSection>
 
== 3D Structures of Aminopeptidase ==
== 3D Structures of Aminopeptidase ==
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[[Aminopeptidase 3D structures]]
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Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
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</StructureSection>
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===Cysteine aminopeptidase===
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[[3pw3]] – PdCys-AP – ''Parabacteroides distasonis''
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===Glutamic acid aminopeptidase===
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-
 
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[[2wyr]] – PhGlu-AP+Co – ''Pyrococcus horikoshii''<br />
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[[3kl9]] – SpGlu-AP – ''Streptococcus pneumoniae''<br />
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[[4kx7]] – hGlu-AP + Zn – human<br />
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[[4kx8]], [[4kxb]] – hGlu-AP + Zn + statin derivative<br />
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[[4kx9]], [[4kxa]], [[4kxc]], [[4kxd]] – hGlu-AP + Zn + amino acid<br />
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-
 
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===Alanine aminopeptidase===
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[[3ebg]] – PfAla-AP - ''Plasmodium falciparum''<br />
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[[3ebh]] - PfAla-AP+bestatin<br />
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[[3ebi]] - PfAla-AP+dipeptide analog<br />
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[[4fke]] – pAla-AP + Zn – pig<br />
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[[4fkh]] – pAla-AP + Zn + alanine<br />
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[[4h5h]], [[4hol]], [[4naq]], [[4nz8]] – pAla-AP + Zn + polyalanine<br />
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[[4hom]] – pAla-AP + Zn + substance P<br />
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[[4fkk]] – pAla-AP + Zn + bestatin<br />
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[[4f5c]] – pAla-AP + PRCV spike protein + Zn<br />
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[[4fyq]] - hAla-AP + Zn <br />
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[[4fyr]] - hAla-AP + Zn + bestatin<br />
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[[4fys]] - hAla-AP + Zn + angiotensin<br />
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[[4fyt]] - hAla-AP + Zn + amastatin<br />
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[[3ked]] – EcAPN+2,4-diaminobutyric acid – ''Escherichia coli''<br />
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[[2hpo]], [[2dq6]], [[3puu]] – EcAPN<br />
+
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[[2hpt]], [[2dqm]] – EcAPN+bestatin<br />
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[[2zxg]] – EcAPN+transition state analog<br />
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[[3b2p]], [[3b2x]], [[3b34]], [[3b37]], [[3b3b]], [[3qjx]] – EcAPN+amino acid<br />
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[[2gtq]] – APN – ''Neisseria meningitides''
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+
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===Proline aminopeptidase===
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[[3ovk]] – Xaa Pro-AP – ''Streptococcus pyogenes''<br />
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[[3il0]] - Xaa Pro-AP – ''Streptococcus thermophilus''<br />
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[[2v3x]], [[2v3y]], [[2v3z]] - Xaa EcPro-AP (mutant)+tripeptide<br />
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[[1w7v]], [[2bh3]] - Xaa EcPro-AP+Zn+Mg+polypeptide<br />
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[[2bn7]] - Xaa EcPro-AP+Zn+Mg+Mn+polypeptide<br />
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[[2bha]], [[2bhd]] - Xaa EcPro-AP+Mg+polypeptide<br />
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[[1a16]] - Xaa EcPro-AP+Mn+polypeptide<br />
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[[1wbq]], [[2bhb]] - Xaa EcPro-AP+Zn+Mg<br />
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[[2bhc]] - Xaa EcPro-AP+Na+Mg<br />
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[[1wl6]] - Xaa EcPro-AP+Mg<br />
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[[1wl9]], [[1m35]], [[1jaw]] - Xaa EcPro-AP+Mn<br />
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[[1wlr]] - Xaa EcPro-AP<br />
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[[2bws]], [[2bwt]], [[2bwu]], [[2bwv]], [[2bww]], [[2bwx]], [[2bwy]] - Xaa EcPro-AP (mutant)<br />
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[[1w2m]] - Xaa EcPro-AP+Ca<br />
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[[1n51]] – Xaa EcPro-AP+apstatin<br />
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[[3ig4]] - Xaa Pro-AP+ Mn – ''Bacillus anthracis''<br />
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[[4fkc]] – Xaa Pro-AP + Cd – ''Thermococcus sibiricus''<br />
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[[2zsg]] – X TmPro-AP – ''Thermatoga maritima''<br />
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[[3ctz]] – X hPro-AP <br />
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[[1x2b]], [[1x2e]], [[1wm1]] – SmPro-AP + inhibitor – ''Serratia marcescens''<br />
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[[1qtr]] – SmPro-AP<br />
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[[1xqv]] – TaPro-AP (mutant) – ''Thermoplasma acidophilum''<br />
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[[1xqw]], [[1xqx]], [[1xqy]], [[1xrl]], [[1xrm]], [[1xrn]], [[1xro]], [[1xrp]], [[1xrq]], [[1xrr]] – TaPro-AP+polypeptide<br />
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[[3azo]] – SmPro-AP – ''Streptomyces morookaensis''<br />
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[[3azp]] - SmPro-AP (mutant)<br />
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[[3azq]] - SmPro-AP (mutant) + PGG<br />
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[[1lns]] – Pro-dipeptidyl-AP – ''Lactococcus lactis''<br />
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[[2z3w]] – PgPro-tripeptidyl-AP (mutant) – ''Porphyromonas gingivalis''<br />
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[[2z3z]] – PgPro-tripeptidyl-AP (mutant) + inhibitor<br />
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===Leucine aminopeptidase===
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+
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[[3jru]] – Leu-AP – ''Xanthomonas oryzae''<br />
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[[2hc9]], [[2hb6]] – Leu-AP – ''Caenorhabditis elegans''<br />
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[[2ewb]] – bLeu-AP+zofenoprilat – bovine<br />
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[[1lam]], [[1lap]] – bLue-AP<br />
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[[1bpm]], [[1bpn]] – bLue-AP+Zn+Mg<br />
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[[2j9a]] - bLue-AP+Zn + inhibitor<br />
+
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[[1lan]], [[1lcp]] – bLue-AP+leucine derivative<br />
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[[1bll]] – bLue-AP+amastatin<br />
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[[2xdt]], [[2yd0]] – hLeu-AP soluble domain <br />
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[[3rjo]] - hLeu-AP peptide-binding domain<br />
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[[3mdj]] - hLeu-AP soluble domain + inhibitor<br />
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[[3h8e]], [[3h8f]], [[3h8g]] – Leu-AP – ''Pseudomonas putida''<br />
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[[3kqx]], [[3kqz]], [[3kr4]], [[3kr5]] – PfLeu-AP <br />
+
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[[3fh4]], [[1rtq]], [[2dea]] – VpLeu-AP – Vibrio proteolyticus<br />
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[[3b35]], [[3b3t]], [[3b3v]], [[2anp]] - VpLeu-AP (mutant)<br />
+
-
[[3b3c]], [[3b3s]], [[3b3w]] - VpLeu-AP (mutant)+Leu derivative<br />
+
-
[[3b7i]] - VpLeu-AP (mutant)+Leu<br />
+
-
[[1ft7]] - VpLeu-AP +Leu derivative<br />
+
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[[3vh9]] - VpLeu-AP + 8-quinolinol<br />
+
-
[[2nyq]], [[2iq6]] – VpLeu-AP+polypeptide<br />
+
-
[[1lok]] – VpLeu-AP+Tris<br />
+
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[[2prq]] – VpLeu-AP+Co<br />
+
-
[[1xry]], [[1txr]] – VpLeu-AP+bestatin<br />
+
-
[[1gyt]] – EcLeu-AP<br />
+
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[[3qnf]] – hLeu-AP 1<br />
+
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[[3t8w]], [[4k3n]] – PfLeu-AP + Zn + inhibitor – ''Plasmodium falciparum''<br />
+
-
[[3tc8]] - PdLeu-AP + Zn<br />
+
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[[4fuu]] - Leu-AP + Zn – ''Bacterioides thetaiotaomicron''<br />
+
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[[4ksi]] – Leu-AP + Mg – tomato<br />
+
-
 
+
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===Methionine aminopeptidase===
+
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+
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[[3mr1]], [[3mx6]] – Met-AP+Mn – ''Rickettsia prowazekii''<br />
+
-
[[2dfi]], [[1xgm]], [[1xgn]], [[1xgo]], [[1xgs]] – PfMet-AP+Co – ''Pyrococcus furiosus''<br />
+
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[[1wkm]] - PfMet-AP+Mn<br />
+
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[[4fo7]] - PaMet-AP+Mn – ''Pseudomonas aeruginosa''<br />
+
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[[4fo8]] - PaMet-AP+Mn + Met <br />
+
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[[4hxx]], [[4iu6]] - hMet-AP+ Co + pyrimidine derivative<br />
+
-
[[3iu7]] – MtMet-AP+Mn +A02 – ''Mycobacterium tuberculosis''<br />
+
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[[3iu8]], [[3iu9]] - MtMet-AP+Ni + inhibitor<br />
+
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[[1yj3]], [[3ror]] - MtMet-AP+Co<br />
+
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[[3pka]] - MtMet-AP+Mn<br />
+
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[[3pkb]], [[3pkc]], [[3pkd]], [[3pke]] - MtMet-AP+bengamide inhibitor<br />
+
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[[3tav]] – Met-AP + Mg – ''Mycobacterium abscessus''< br />
+
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[[1y1n]] - MtMet-AP+K<br />
+
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[[4idy]], [[4iec]] - MtMet-AP+K + hydroxyethyl disulfide<br />
+
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[[4if7]] - MtMet-AP+K + homocysteinemethyl disulfide<br />
+
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[[3fm3]] – EncMet-AP – ''Encephalitozoon cuniculi''<br />
+
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[[3fmq]], [[3fmr]] - EncMet-AP+angiogenesis inhibitor<br />
+
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[[3d27]], [[2q92]], [[2q93]], [[2q94]], [[2q95]], [[2q96]], [[2p98]], [[2p99]], [[2p9a]], [[2gu4]], [[2gu5]], [[2gu6]], [[2evc]], [[2evm]], [[2evo]], [[2bbv]], [[1xnz]], [[4a6v]], [[4a6w]], [[2bb7]] – EcMet-AP+Mn+inhibitor<br />
+
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[[2gg0]], [[2gg2]], [[2gg3]], [[2gg5]], [[2gg7]], [[2gg8]], [[2gg9]], [[2ggb]], [[2ggc]] - EcMet-AP+Co+inhibitor<br />
+
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[[1c21]], [[1c22]], [[1c23]], [[1c24]] - EcMet-AP +Co + methionine derivative<br />
+
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[[1c27]] - EcMet-AP +Co +norleucine<br />
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[[3tb5]] – Met-AP – ''Enterococcus faecalis''<br />
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[[2ea2]], [[2ea4]], [[2ga2]], [[2nq6]], [[2nq7]], [[1yw7]], [[1yw8]], [[1yw9]] - hMet-AP+Mn+inhibitor<br />
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[[2gtx]], [[2gu7]] – EcMet-AP<br />
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[[1yvm]] – EcMet-AP (mutant)+Co+thiabendazole<br />
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[[1mat]] – EcMet-AP+Co<br />
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[[2mat]], [[4mat]] - EcMet-AP (mutant)+Co<br />
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[[3mat]] - EcMet-AP (mutant)+Co+bestatin derivative<br />
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[[2b3h]], [[2b3k]] - hMet-AP+Co<br />
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[[1boa]] - hMet-AP+Co+ angiogenesis inhibitor<br />
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[[2b3l]] – hMet-AP<br />
+
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[[1kq0]], [[1kq9]] – hMet-AP+methionine<br />
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[[2gz5]], [[2adu]], [[1qzy]], [[1b59]], [[1b6a]], [[1bn5]], [[2oaz]], [[4ikr]], [[4iks]], [[4ikt]], [[4iku]] – hMet-AP+Co+inhibitor<br />
+
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[[1r58]], [[1r5g]], [[1r5h]], [[4fli]], [[4flj]], [[4flk]], [[4fll]] - hMet-AP+Mn+inhibitor<br />
+
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[[2g6p]] - hMet-AP truncated+Mn+inhibitor<br />
+
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[[1qxw]], [[1qxy]], [[1qxz]] – Met-AP+Co+inhibitor - ''Staphylococcus aureus''<br />
+
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[[1o0x]] – TmMet-AP<br />
+
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[[3s6b]] – PfMet-AP + Fe <br />
+
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[[4fuk]] – TbMet-AP + Zn – ''Trypanosoma brucei''<br />
+
-
[[4km3]] – SpAP<br />
+
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+
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===Arginine aminopeptidase===
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+
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[[4jbs]] – hArg-AP+ Zn + inhibitor<br />
+
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===Aspartic acid aminopeptidase===
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+
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[[3l6s]], [[4dyo]] – hAsp-AP+aspartic hydroxamate<br />
+
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[[3var]], [[3vat]] – bAsp-AP<br />
+
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[[4eme]] – PfAsp-AP + Zn
+
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+
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===Asparagine aminopeptidase===
+
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+
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[[3c17]], [[2zak]] – EcAsn-AP (mutant)<br />
+
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[[2zal]] – EcAsn-AP+Asp<br />
+
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[[2gez]] – Asn-AP – ''Lupinus luteus''
+
-
 
+
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===Serine aminopeptidase===
+
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+
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[[1b65]] – OaSer-AP – ''Ochrobactrum anthropi''
+
-
 
+
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===Cytosolic aminopeptidase===
+
-
 
+
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[[3pei]] – Cyt-AP – ''Francisella tularensis''<br />
+
-
[[3kzw]] – Cyt-AP – ''Staphylococcus aureus''<br />
+
-
[[3ij3]] – Cyt-AP – ''Coxiella burnetii''
+
-
 
+
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===Aminopeptidase 2===
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+
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[[3se6]] – hAPN<br />
+
-
[[4e36]] – hAPN + Zn
+
-
 
+
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===Non-specific aminopeptidase===
+
-
 
+
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[[2ek8]] – AnAP – Aneurinibacillus<br />
+
-
[[2ek9]] – AnAP+bestatin<br />
+
-
[[1y0r]], [[1xfo]] – PhAP<br />
+
-
[[1y0y]] – PhAP+amastatin<br />
+
-
[[1amp]] - VpAP<br />
+
-
[[1cp6]], [[1igb]] – VpAP+inhibitor<br />
+
-
[[1ei5]] – OaAP<br />
+
-
[[3edy]], [[3ee6]] – hTripeptidyl-AP <br />
+
-
[[3zn8]] – Dipeptidyl-AP B + signal recognition particle protein + signal recognition particle receptor + RNA – yeast<br />
+
-
[[4efd]] – TbAP M17 + Mn<br />
+
-
[[4fgm]] – AP N + Zn – ''Idiomarina loihiensis''<br />
+
-
[[4icq]] – SpAP Peps + Zn<br />
+
-
[[4icr]] – SpAP Peps (mutant) + Zn<br />
+
-
[[4ics]] – SpAP Peps (mutant) + Zn + Trp + Gly<br />
+
-
 
+
-
===Cold-activated aminopeptidase===
+
-
 
+
-
[[3cia]] – Col-AP – ''Colwellia psychrerythraea''
+
-
 
+
-
===Deblocking aminopeptidase===
+
-
 
+
-
[[2gre]] – DAP – ''Bacillus cereus''
+
-
 
+
-
===Heat stable aminopeptidase===
+
-
 
+
-
[[2ayi]] – AmpT – ''Thermus thermophilus''
+
-
 
+
-
===Aminopeptidase from ''Staphylococcus aureus''===
+
-
 
+
-
[[1zjc]] - AmpS
+
-
 
+
-
===Metalloaminopeptidase===
+
-
 
+
-
[[3q43]], [[3q44]] – PfPFAP (mutant) + bestatin derivative<br />
+
-
 
+
-
===''Stereomyces griesus'' aminopeptidase===
+
-
 
+
-
[[1xjo]], [[1cp7]] - SGAP<br />
+
-
[[1qq9]], [[1f2o]], [[1f2p]], [[1tf8]], [[1tf9]], [[1tkf]], [[1tkh]], [[1tkj]], [[1xbu]] - SGAP + amino acid
+
-
 
+
-
===β-peptidyl aminopeptidase===
+
-
 
+
-
[[3n2w]] – SxBapA – ''Sphingosinicella xenopeptidilytica''<br />
+
-
[[3n5i]] – SxBapA (mutant)<br />
+
-
[[3n33]] – SxBapA + AEBSF<br />
+
-
[[3ndv]], [[3nfb]] – SxBapA + ampicillin
+
-
 
+
-
===M1 family aminopeptidase===
+
-
 
+
-
[[4j3b]] – PfAP (mutant)<br />
+
-
[[3t8v]] – PfAP M1<br />
+
-
[[4k5l]], [[4k5m]], [[4k5n]], [[4k5p]], [[4k5o]] - PfLeu-AP (mutant) + Zn + inhibitor<br />
+
-
===Aminopeptidase C===
 
-
[[4k7c]] – AP – ''Lactobacillus rahmnosis''<br />
 
{{Clear}}
{{Clear}}

Current revision

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 Resources

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

References

  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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