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A Novel Factor Xa-Inhibiting Peptide from Centipedes Venom.

Kong Y, Shao Y, Chen H, Ming X, Wang JB, Li ZY, Wei JF - Int J Pept Res Ther (2013)

Bottom Line: It prolonged the partial thromboplastin time and prothrombin time in both in vitro and ex vivo assays.It also significantly prolonged whole blood clotting time and bleeding time in mice.This is the first report that an FXa inhibiting peptide was isolated from centipedes venom.

View Article: PubMed Central - PubMed

Affiliation: School of Life Science & Technology, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing, 210009 People's Republic of China ; State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009 People's Republic of China.

ABSTRACT
Centipedes have been used as traditional medicine for thousands of years in China. Centipede venoms consist of many biochemical peptides and proteins. Factor Xa (FXa) is a serine endopeptidase that plays the key role in blood coagulation, and has been used as a new target for anti-thrombotic drug development. A novel FXa inhibitor, a natural peptide with the sequence of Thr-Asn-Gly-Tyr-Thr (TNGYT), was isolated from the venom of Scolopendra subspinipes mutilans using a combination of size-exclusion and reverse-phase chromatography. The molecular weight of the TNGYT peptide was 554.3 Da measured by electrospray ionization mass spectrometry. The amino acid sequence of TNGYT was determined by Edman degradation. TNGYT inhibited the activity of FXa in a dose-dependent manner with an IC50 value of 41.14 mg/ml. It prolonged the partial thromboplastin time and prothrombin time in both in vitro and ex vivo assays. It also significantly prolonged whole blood clotting time and bleeding time in mice. This is the first report that an FXa inhibiting peptide was isolated from centipedes venom.

No MeSH data available.


Molecular docking of TNGYT with FXa. TNGYT bound to Asp189, Ser195 and Tyr228 residues of S1 and Tyr99 residue of S4 of FXa
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Fig5: Molecular docking of TNGYT with FXa. TNGYT bound to Asp189, Ser195 and Tyr228 residues of S1 and Tyr99 residue of S4 of FXa

Mentions: FXa contains a deep S1 pocket and a box-like S4 pocket at the active site. S1 pocket consists of Asp189, Ser195 and Tyr228 residues while S4 consists of Tyr99, Phe174 and Trp228 residues. Potential FXa inhibitors usually bind to both S1 and S4 pockets which are connected in L-shape (Rai et al. 2001). As shown in Fig. 5, it was found that TNGYT binds to Asp189, Ser195 and Tyr228 residues of S1 and Tyr99 residue of S4 at the MM/GBVI value of −17.696 kcal/mol. This docking result supported the result of FXa inhibition assay and confirmed that TNGYT is an FXa inhibitor.Fig. 5


A Novel Factor Xa-Inhibiting Peptide from Centipedes Venom.

Kong Y, Shao Y, Chen H, Ming X, Wang JB, Li ZY, Wei JF - Int J Pept Res Ther (2013)

Molecular docking of TNGYT with FXa. TNGYT bound to Asp189, Ser195 and Tyr228 residues of S1 and Tyr99 residue of S4 of FXa
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3824214&req=5

Fig5: Molecular docking of TNGYT with FXa. TNGYT bound to Asp189, Ser195 and Tyr228 residues of S1 and Tyr99 residue of S4 of FXa
Mentions: FXa contains a deep S1 pocket and a box-like S4 pocket at the active site. S1 pocket consists of Asp189, Ser195 and Tyr228 residues while S4 consists of Tyr99, Phe174 and Trp228 residues. Potential FXa inhibitors usually bind to both S1 and S4 pockets which are connected in L-shape (Rai et al. 2001). As shown in Fig. 5, it was found that TNGYT binds to Asp189, Ser195 and Tyr228 residues of S1 and Tyr99 residue of S4 at the MM/GBVI value of −17.696 kcal/mol. This docking result supported the result of FXa inhibition assay and confirmed that TNGYT is an FXa inhibitor.Fig. 5

Bottom Line: It prolonged the partial thromboplastin time and prothrombin time in both in vitro and ex vivo assays.It also significantly prolonged whole blood clotting time and bleeding time in mice.This is the first report that an FXa inhibiting peptide was isolated from centipedes venom.

View Article: PubMed Central - PubMed

Affiliation: School of Life Science & Technology, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing, 210009 People's Republic of China ; State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009 People's Republic of China.

ABSTRACT
Centipedes have been used as traditional medicine for thousands of years in China. Centipede venoms consist of many biochemical peptides and proteins. Factor Xa (FXa) is a serine endopeptidase that plays the key role in blood coagulation, and has been used as a new target for anti-thrombotic drug development. A novel FXa inhibitor, a natural peptide with the sequence of Thr-Asn-Gly-Tyr-Thr (TNGYT), was isolated from the venom of Scolopendra subspinipes mutilans using a combination of size-exclusion and reverse-phase chromatography. The molecular weight of the TNGYT peptide was 554.3 Da measured by electrospray ionization mass spectrometry. The amino acid sequence of TNGYT was determined by Edman degradation. TNGYT inhibited the activity of FXa in a dose-dependent manner with an IC50 value of 41.14 mg/ml. It prolonged the partial thromboplastin time and prothrombin time in both in vitro and ex vivo assays. It also significantly prolonged whole blood clotting time and bleeding time in mice. This is the first report that an FXa inhibiting peptide was isolated from centipedes venom.

No MeSH data available.