Peptide name : (Bl- LAAO) L-amino acid oxidases (L-AAO)

Source/Organism : Venom base

Linear/Cyclic : Linear

Chirality : L

Peptide length: 30

C-terminal modification: Linear

N-terminal modification : Not found

Non-natural peptide information: None

Assay type : MTT assay

Assay time : 24h

Activity : Not found

Cell line : MKN-45

Cancer type : Stomach cancer

Other activity : Not found

Amino acid composition bar chart :

Molecular mass : 3506.7158 Dalton

Aliphatic index : 0.586

Instability index : 42.7533

Hydrophobicity (GRAVY) : -1

Isoelectric point : 4.0563

Charge (pH 7) : -6.1958

Aromaticity : 0.1

Molar extinction coefficient (cysteine, cystine): (1490, 1490)

Hydrophobic/hydrophilic ratio : 0.57894736

hydrophobic moment : 0.2301

Missing amino acid : W,H,Q,M,V

Most occurring amino acid : E

Most occurring amino acid frequency : 6

Least occurring amino acid : P

Least occurring amino acid frequency : 1

Secondary structure fraction (Helix, Turn, Sheet): (0.4, 0.2, 0.3)

SMILES Notation: CC[C@H](C)[C@H](NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](CC(=O)O)NC(=O)[C@@H](NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](CS)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](C)N)[C@@H](C)O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@H](C(=O)O)[C@@H](C)O)[C@@H](C)O

1 : Naumann GB, et al. Cytotoxicity and inhibition of platelet aggregation caused by an l-amino acid oxidase from Bothrops leucurus venom. Biochim Biophys Acta. 2011; 1810:683-94. doi: 10.1016/j.bbagen.2011.04.003

Paper title : Cytotoxicity and inhibition of platelet aggregation caused by an l-amino acid oxidase from Bothrops leucurus venom.

Doi : https://doi.org/10.1016/j.bbagen.2011.04.003

Abstract : BACKGROUND: Multifunctional l-amino acid oxidases (LAAOs) occur widely in snake venoms. METHODS: The l-AAO from Bothrops leucurus (Bl-LAAO) venom was purified using a combination of molecular exclusion and ion-exchange chromatographies. We report some biochemical features of Bl-LAAO associated with its effect on platelet function and its cytotoxicity. RESULTS: Bl-LAAO is a 60kDa monomeric glycoprotein. Its N-terminal sequence shows high homology to other members of the snake-venom LAAO family. Bl-LAAO catalyzes oxidative deamination of l-amino acids with the generation of H₂O₂. The best substrates were: l-Met, l-Norleu, l-Leu, l-Phe and l-Trp. The effects of snake venom LAAOs in hemostasis, especially their action on platelet function remain largely unknown. Bl-LAAO dose-dependently inhibited platelet aggregation of both human PRP and washed platelets. Moreover, the purified enzyme exhibited a killing effect in vitro against Leishmania sp., promastigotes, with a very low EC(50) of 0.07μM. Furthermore, the cytotoxicity of Bl-LAAO was observed in the stomach cancer MKN-45, adeno carcinoma HUTU, colorectal RKO and human fibroblast LL-24 cell lines. The enzyme released enough H₂O₂ in culture medium to induce apoptosis in cells in a dose- and time-dependent manner. The biological effects were inhibited by catalase. CONCLUSION: Bl-LAAO, a major component of B. leucurus venom, is a cytotoxin acting primarily via the generation of high amounts of H₂O₂ which kill the cells. GENERAL SIGNIFICANCE: These results allow us to consider the use of LAAOs as anticancer agents, as tools in biochemical studies to investigate cellular processes, and to obtain a better understanding of the envenomation mechanism.