Aminopeptidase

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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 SGAP (1xjo). 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.

3D Structures of Aminopeptidase

Update November 2011

Cysteine aminopeptidase

3pw3 – PdCys-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
3ig4 - Xaa Pro-AP+ Mn – Bacillus anthracis
2zsg – X TmPro-AP – Thermatoga maritima
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
3azo – SmPro-AP – Streptomyces morookaensis
3azp - SmPro-AP (mutant)
3azq - SmPro-AP (mutant) + PGG

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, 2yd0 – hLeu-AP soluble domain
3mdj - hLeu-AP soluble domain + inhibitor
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
3b7i - VpLeu-AP (mutant)+Leu
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
3qnf – hLeu-AP 1
3t8w – PfLeu-AP + Zn + inhibitor – Plasmodium falciparum
3tc8 - PdLeu-AP + Zn

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
3pka - MtMet-AP+Mn
3pkb, 3pkc, 3pkd, 3pke - MtMet-AP+bengamide inhibitor
3tav – Met-AP + Mg – Mycobacterium abscessus< br /> 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
3s6b – PfMet-AP + Fe

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
3t8v – PfAP M1

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

Stereomyces griesus aminopeptidase

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

β-peptidyl AP

3n2w – SxBapA – Sphingosinicella xenopeptidilytica
3n5i – SxBapA (mutant)
3n33 – SxBapA + AEBSF
3ndv, 3nfb – SxBapA + ampicillin

S. griseus aminopeptidase

spinqualitylabelsall models 1xjo Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

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
Streptomyces griseus Aminopeptidase (SGAP)