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Literature summary for 3.4.11.10 extracted from

  • Modak, J.K.; Rut, W.; Wijeyewickrema, L.C.; Pike, R.N.; Drag, M.; Roujeinikova, A.
    Structural basis for substrate specificity of Helicobacter pylori M17 aminopeptidase (2016), Biochimie, 121, 60-71 .
    View publication on PubMed

Crystallization (Commentary)

Crystallization (Comment) Organism
purified enzyme free and in complex with inhibitor bestatin, enzyme bound with Zn2+ and Na+, hanging drop vapour-diffusion method, mixing of 0.002 ml of 11.2 mg/ml protein solution with 0.002 ml of reservoir solution containing 11% w/v PEG 3350 and 100 mM sodium formate, pH 7.0, and equilibration against reservoir solution, crystals of HpM17AP-bestatin complex are obtained by using 5.6 mg/ml protein, 1 mM bestatin and the reservoir solution containing 12% w/v PEG 2000 and 100 mM sodium formate, pH 7.0, 19°C, X-ray diffraction structure determination and analysis at 1.9-2.0 A resolution, molecular replacement using the structure of LAP from Pseudomonas putida (PDB ID 3h8g) as a search model Helicobacter pylori

Inhibitors

Inhibitors Comment Organism Structure
bestatin (2S)-2-[[(2S,3R)-3-amino-2-hydroxy-4-phenylbutanoyl]amino]-4-methylpentanoic acid, inhibits HpM17AP and suppresses Helicobacter pylori growth, enzyme binding structure analysis from the crystal structures of HpM17AP and its complex with bestatin. The position of the D-phenylalanine moiety of the inhibitor with respect to the active-site metal ions, bicarbonate ion and with respect to other M17 aminopeptidases suggests that this residue binds to the S1 subsite of HpM17AP Helicobacter pylori
EDTA
-
Helicobacter pylori

Metals/Ions

Metals/Ions Comment Organism Structure
Mn2+ required Helicobacter pylori
Na+ the sodium ion is coordinated by the main-chain carbonyl oxygen atoms of A461, G462, Y465 and three water molecules in an octahedral geometry Helicobacter pylori
Zn2+ two active-site positively charged zinc ions are coordinated by negatively charged side-chain oxygen atoms of three aspartate residues (D263, D281, D340) and one glutamate residue (E342), the side-chain nitrogen atom of K258 and two water molecules in a distorted octahedral coordination geometry Helicobacter pylori

Organism

Organism UniProt Comment Textmining
Helicobacter pylori O25294 i.e. Campylobacter pylori
-
Helicobacter pylori 26695 O25294 i.e. Campylobacter pylori
-
Helicobacter pylori ATCC 700392 O25294 i.e. Campylobacter pylori
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
L-arginyl 7-amido-4-carbamoylmethylcoumarin + H2O
-
Helicobacter pylori L-arginine + 7-amino-4-carbamoylmethylcoumarin
-
?
L-arginyl 7-amido-4-carbamoylmethylcoumarin + H2O
-
Helicobacter pylori ATCC 700392 L-arginine + 7-amino-4-carbamoylmethylcoumarin
-
?
L-arginyl 7-amido-4-carbamoylmethylcoumarin + H2O
-
Helicobacter pylori 26695 L-arginine + 7-amino-4-carbamoylmethylcoumarin
-
?
L-cysteinyl 7-amido-4-carbamoylmethylcoumarin + H2O
-
Helicobacter pylori L-cysteine + 7-amino-4-carbamoylmethylcoumarin
-
?
L-cysteinyl 7-amido-4-carbamoylmethylcoumarin + H2O
-
Helicobacter pylori ATCC 700392 L-cysteine + 7-amino-4-carbamoylmethylcoumarin
-
?
L-cysteinyl 7-amido-4-carbamoylmethylcoumarin + H2O
-
Helicobacter pylori 26695 L-cysteine + 7-amino-4-carbamoylmethylcoumarin
-
?
L-leucyl 7-amido-4-carbamoylmethylcoumarin + H2O
-
Helicobacter pylori L-leucine + 7-amino-4-carbamoylmethylcoumarin
-
?
L-leucyl 7-amido-4-carbamoylmethylcoumarin + H2O
-
Helicobacter pylori ATCC 700392 L-leucine + 7-amino-4-carbamoylmethylcoumarin
-
?
L-leucyl 7-amido-4-carbamoylmethylcoumarin + H2O
-
Helicobacter pylori 26695 L-leucine + 7-amino-4-carbamoylmethylcoumarin
-
?
L-methionyl 7-amido-4-carbamoylmethylcoumarin + H2O
-
Helicobacter pylori L-methionine + 7-amino-4-carbamoylmethylcoumarin
-
?
L-methionyl 7-amido-4-carbamoylmethylcoumarin + H2O
-
Helicobacter pylori ATCC 700392 L-methionine + 7-amino-4-carbamoylmethylcoumarin
-
?
L-methionyl 7-amido-4-carbamoylmethylcoumarin + H2O
-
Helicobacter pylori 26695 L-methionine + 7-amino-4-carbamoylmethylcoumarin
-
?
additional information substrate specificity of HpM17AP, overview Helicobacter pylori ?
-
?
additional information substrate specificity of HpM17AP, overview Helicobacter pylori ATCC 700392 ?
-
?
additional information substrate specificity of HpM17AP, overview Helicobacter pylori 26695 ?
-
?

Subunits

Subunits Comment Organism
More the HpM17AP subunit consists of a single polypeptide chain of 496 residues and comprises a total of 14 alpha-helices and 16 beta-strands, which account for 39% and 15% of the total residues, respectively. Like other M17 aminopeptidases, HpM17AP folds into two domains of a mixed alpha/beta structure connected via a long helix alpha4. The N-terminal domain comprises residues 1 to 155, the connecting helix runs from residue 156 to 182 and the C-terminal domain comprises residues 183 to 496. Residues 97-103 and 147-154 are not included in the model due to poorly defined electron density. Topology of the secondary structure elements, overview Helicobacter pylori

Synonyms

Synonyms Comment Organism
bacterial M17 aminopeptidase
-
Helicobacter pylori
HpM17AP
-
Helicobacter pylori
M17 aminopeptidase
-
Helicobacter pylori
PepA
-
Helicobacter pylori

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
37
-
assay at Helicobacter pylori

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
8
-
assay at Helicobacter pylori

General Information

General Information Comment Organism
additional information structural basis of catalysis and inhibition of the enzyme, active site of the free enzyme, overview Helicobacter pylori
physiological function the M17 aminopeptidase from the carcinogenic gastric bacterium Helicobacter pylori (HpM17AP) is an important housekeeping enzyme involved in catabolism of endogenous and exogenous peptides. It is implicated in Helicobacter pylori defence against the human innate immune response and in the mechanism of metronidazole resistance Helicobacter pylori