Aminopeptidase

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{{STRUCTURE_1xjo| PDB=1xjo | SIZE=300| SCENE= |right|CAPTION=Aminopeptidase [[1xjo]] }}
{{STRUCTURE_1xjo| PDB=1xjo | SIZE=300| SCENE= |right|CAPTION=Aminopeptidase [[1xjo]] }}
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'''Aminopeptidases''' catalyze a release of an N-terminal amino acid from a peptide, amide, or arylamide.
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[[Aminopeptidase|Aminopeptidases]] (AP) 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. The images at the left and at the right correspond to one representative Aminopeptidase, ''i.e.'' the crystal structure of ''Stereomyces griesus'' aminopeptidase ([[1xjo]]).
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{{TOC limit|limit=2}}
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== 3D Structures of Aminopeptidase ==
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===Cysteine aminopeptidase===
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[[3pw3]] – Cys-AP – ''Parabacteroides distasonis''
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===Glutamic acid aminopeptidase===
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[[2wyr]] – PhGlu-AP+Co – ''Pyrococcus horikoshii''<br />
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[[3kl9]] – Glu-AP – ''Streptococcus pneumoniae''
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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
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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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[[1wi9]], [[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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[[2zsg]] – X TmPro-AP – ''Thermatoga maritime''<br />
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[[3ctz]] – X hPro-AP – human<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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===Leucine aminopeptidase===
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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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[[1lan]], [[1lcp]] – bLue-AP+leucine derivative<br />
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[[1bll]] – bLue-AP+amastatin<br />
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[[2xdt]] – hLeu-AP soluble domain <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 />
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[[3b3c]], [[3b3s]], [[3b3w]] - VpLeu-AP (mutant)+Leu derivative<br />
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[[1ft7]] - VpLeu-AP +Leu derivative<br />
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[[2nyq]], [[2iq6]] – VpLeu-AP+polypeptide<br />
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[[1lok]] – VpLeu-AP+Tris<br />
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[[2prq]] – VpLeu-AP+Co<br />
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[[1xry]], [[1txr]] – VpLeu-AP+bestatin<br />
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[[1gyt]] – EcLeu-AP
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===Methionine aminopeptidase===
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[[3mr1]], [[3mx6]] – Met-AP+Mn – ''Rickettsia prowazekii''<br />
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[[2dfi]], [[1xgm]], [[1xgn]], [[1xgo]], [[1xgs]] – PfMet-AP+Co – ''Pyrococcus furiosus''<br />
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[[1wkm]] - PfMet-AP+Mn<br />
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[[3iu7]] – MtMet-AP+Mn +A02 – ''Mycobacterium tuberculosis''<br />
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[[3iu8]], [[3iu9]] - MtMet-AP+Ni + inhibitor<br />
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[[1yj3]] - MtMet-AP+Co<br />
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[[1y1n]] - MtMet-AP+K<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]] – 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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[[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]] – hMet-AP+Co+inhibitor<br />
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[[1r58]], [[1r5g]], [[1r5h]] - 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
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===Aspartic acid aminopeptidase===
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[[3l6s]] – hAsp-AP+aspartic hydroxamate
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===Asparagine aminopeptidase===
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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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[[1b65]] – Ser-AP – ''Ochrobactrum anthropi''
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===Cytosolic aminopeptidase===
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[[3pei]] – Cyt-AP – ''Francisella tularensis''<br />
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[[3kzw]] – Cyt-AP – ''Staphylococcus aureus''<br />
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[[3ij3]] – Cyt-AP – ''Coxiella burnetii''
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===Aminopeptidase N===
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[[3ked]] – EcAPN+2,4-diaminobutyric acid – ''Escherichia coli''<br />
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[[2hpo]], [[2dq6]] – 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]] – EcAPN+amino acid<br />
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[[2gtq]] – APN – ''Neisseria meningitides''
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===Non-specific aminopeptidase===
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[[2ek8]] – AnAP – Aneurinibacillus<br />
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[[2ek9]] – AnAP+bestatin<br />
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[[1y0r]], [[1xfo]] – PhAP<br />
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[[1y0y]] – PhAP+amastatin<br />
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[[1amp]] - VpAP<br />
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[[1cp6]], [[1igb]] – VpAP+inhibitor
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===Cold-activated aminopeptidase===
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[[3cia]] – Col-AP – ''Colwellia psychrerythraea''
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===Deblocking aminopeptidase===
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[[2gre]] – DAP – ''Bacillus cereus''
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===Heat stable aminopeptidase===
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[[2ayi]] – AmpT – ''Thermus thermophilus''
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===Aminopeptidase from ''Staphylococcus aureus''===
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[[1zjc]] - AmpS
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===''Stereomyces griesus'' aminopeptidase===
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[[1xjo]], [[1cp7]] - SGAP
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[[1qq9]], [[1f2o]], [[1f2p]], [[1tf8]], [[1tf9]], [[1tkf]], [[1tkh]], [[1tkj]], [[1xbu]] - SGAP + amino acid
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{{Clear}}
{{Clear}}
== ''S. griseus'' aminopeptidase ==
== ''S. griseus'' aminopeptidase ==

Revision as of 12:09, 30 December 2010

Crystal Structure of Aminopeptidase 1xjo
Crystal Structure of Aminopeptidase 1xjo

Template:STRUCTURE 1xjo

Aminopeptidases (AP) 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. The images at the left and at the right correspond to one representative Aminopeptidase, i.e. the crystal structure of Stereomyces griesus aminopeptidase (1xjo).

3D Structures of Aminopeptidase

Cysteine aminopeptidase

3pw3 – Cys-AP – Parabacteroides distasonis

Glutamic acid aminopeptidase

2wyr – PhGlu-AP+Co – Pyrococcus horikoshii
3kl9 – Glu-AP – Streptococcus pneumoniae

Alanine aminopeptidase

3ebg – PfAla-AP - Plasmodium falciparum
3ebh - PfAla-AP+bestatin
3ebi - PfAla-AP+dipeptide analog

Proline aminopeptidase

3ovk – Xaa Pro-AP – Streptococcus pyogenes
3il0 - Xaa Pro-AP – Streptococcus thermophilus
2v3x, 2v3y, 2v3z - Xaa EcPro-AP (mutant)+tripeptide
1w7v, 2bh3 - Xaa EcPro-AP+Zn+Mg+polypeptide
2bn7 - Xaa EcPro-AP+Zn+Mg+Mn+polypeptide
2bha, 2bhd - Xaa EcPro-AP+Mg+polypeptide
1a16 - Xaa EcPro-AP+Mn+polypeptide
1wbq, 2bhb - Xaa EcPro-AP+Zn+Mg
2bhc - Xaa EcPro-AP+Na+Mg
1wl6 - Xaa EcPro-AP+Mg
1wi9, 1m35, 1jaw - Xaa EcPro-AP+Mn
1wlr - Xaa EcPro-AP
2bws, 2bwt, 2bwu, 2bwv, 2bww, 2bwx, 2bwy - Xaa EcPro-AP (mutant)
1w2m - Xaa EcPro-AP+Ca
1n51 – Xaa EcPro-AP+apstatin
2zsg – X TmPro-AP – Thermatoga maritime
3ctz – X hPro-AP – human
1x2b, 1x2e, 1wm1 – SmPro-AP + inhibitor – Serratia marcescens
1qtr – SmPro-AP
1xqv – TaPro-AP (mutant) – Thermoplasma acidophilum
1xqw, 1xqx, 1xqy, 1xrl, 1xrm, 1xrn, 1xro, 1xrp, 1xrq, 1xrr – TaPro-AP+polypeptide

Leucine aminopeptidase

3jru – Leu-AP – Xanthomonas oryzae
2hc9, 2hb6 – Leu-AP – Caenorhabditis elegans
2ewb – bLeu-AP+zofenoprilat – bovine
1lam, 1lap – bLue-AP
1bpm, 1bpn – bLue-AP+Zn+Mg
1lan, 1lcp – bLue-AP+leucine derivative
1bll – bLue-AP+amastatin
2xdt – hLeu-AP soluble domain
3h8e, 3h8f, 3h8g – Leu-AP – Pseudomonas putida
3kqx, 3kqz, 3kr4, 3kr5 – PfLeu-AP
3fh4, 1rtq, 2dea – VpLeu-AP – Vibrio proteolyticus
3b35, 3b3t, 3b3v, 2anp - VpLeu-AP (mutant)
3b3c, 3b3s, 3b3w - VpLeu-AP (mutant)+Leu derivative
1ft7 - VpLeu-AP +Leu derivative
2nyq, 2iq6 – VpLeu-AP+polypeptide
1lok – VpLeu-AP+Tris
2prq – VpLeu-AP+Co
1xry, 1txr – VpLeu-AP+bestatin
1gyt – EcLeu-AP

Methionine aminopeptidase

3mr1, 3mx6 – Met-AP+Mn – Rickettsia prowazekii
2dfi, 1xgm, 1xgn, 1xgo, 1xgs – PfMet-AP+Co – Pyrococcus furiosus
1wkm - PfMet-AP+Mn
3iu7 – MtMet-AP+Mn +A02 – Mycobacterium tuberculosis
3iu8, 3iu9 - MtMet-AP+Ni + inhibitor
1yj3 - MtMet-AP+Co
1y1n - MtMet-AP+K
3fm3 – EncMet-AP – Encephalitozoon cuniculi
3fmq, 3fmr - EncMet-AP+angiogenesis inhibitor
3d27, 2q92, 2q93, 2q94, 2q95, 2q96, 2p98, 2p99, 2p9a, 2gu4, 2gu5, 2gu6, 2evc, 2evm, 2evo, 2bbv, 1xnz – EcMet-AP+Mn+inhibitor
2gg0, 2gg2, 2gg3, 2gg5, 2gg7, 2gg8, 2gg9, 2ggb, 2ggc - EcMet-AP+Co+inhibitor
1c21, 1c22, 1c23, 1c24 - EcMet-AP +Co + methionine derivative
1c27 - EcMet-AP +Co +norleucine
2ea2, 2ea4, 2ga2, 2nq6, 2nq7, 1yw7, 1yw8, 1yw9 - hMet-AP+Mn+inhibitor
2gtx, 2gu7 – EcMet-AP
1yvm – EcMet-AP (mutant)+Co+thiabendazole
1mat – EcMet-AP+Co
2mat, 4mat - EcMet-AP (mutant)+Co
3mat - EcMet-AP (mutant)+Co+bestatin derivative
2b3h, 2b3k - hMet-AP+Co
1boa - hMet-AP+Co+ angiogenesis inhibitor
2b3l – hMet-AP
1kq0, 1kq9 – hMet-AP+methionine
2gz5, 2adu, 1qzy, 1b59, 1b6a, 1bn5 – hMet-AP+Co+inhibitor
1r58, 1r5g, 1r5h - hMet-AP+Mn+inhibitor
2g6p - hMet-AP truncated+Mn+inhibitor
1qxw, 1qxy, 1qxz – Met-AP+Co+inhibitor - Staphylococcus aureus
1o0x – TmMet-AP

Aspartic acid aminopeptidase

3l6s – hAsp-AP+aspartic hydroxamate

Asparagine aminopeptidase

3c17, 2zak – EcAsn-AP (mutant)
2zal – EcAsn-AP+Asp
2gez – Asn-AP – Lupinus luteus

Serine aminopeptidase

1b65 – Ser-AP – Ochrobactrum anthropi

Cytosolic aminopeptidase

3pei – Cyt-AP – Francisella tularensis
3kzw – Cyt-AP – Staphylococcus aureus
3ij3 – Cyt-AP – Coxiella burnetii

Aminopeptidase N

3ked – EcAPN+2,4-diaminobutyric acid – Escherichia coli
2hpo, 2dq6 – EcAPN
2hpt, 2dqm – EcAPN+bestatin
2zxg – EcAPN+transition state analog
3b2p, 3b2x, 3b34, 3b37, 3b3b – EcAPN+amino acid
2gtq – APN – Neisseria meningitides

Non-specific aminopeptidase

2ek8 – AnAP – Aneurinibacillus
2ek9 – AnAP+bestatin
1y0r, 1xfo – PhAP
1y0y – PhAP+amastatin
1amp - VpAP
1cp6, 1igb – VpAP+inhibitor

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

Stereomyces griesus aminopeptidase

1xjo, 1cp7 - SGAP 1qq9, 1f2o, 1f2p, 1tf8, 1tf9, 1tkf, 1tkh, 1tkj, 1xbu - SGAP + amino acid

S. griseus aminopeptidase

1xjo

Drag the structure with the mouse to rotate

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.

Additional Resources

For additional information, see: Amino Acid Synthesis & Metabolism

Proteopedia Page Contributors and Editors (what is this?)

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

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