3ubu

Crystal structure of agkisacucetin, a GpIb-binding snaclec (snake C-type lectin) that inhibits plateletCrystal structure of agkisacucetin, a GpIb-binding snaclec (snake C-type lectin) that inhibits platelet

Structural highlights

3ubu is a 2 chain structure with sequence from Deinagkistrodon acutus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
NonStd Res:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[SLA1_DEIAC] Agglucetin specifically causes platelet aggregation and surface exposure of integrin alpha-IIb/beta-3 with a GPIb-(GP1BA-) dependent manner in washed platelets. It binds to human platelets in a saturable manner, and its binding is specifically blocked by anti-GP Ib mAb. It regulates endothelial cell survival and promotes angiogenesis by activating integrin alpha-v/beta-3 signaling through FAK/phosphatidylinositol 3-kinase (PI3K)/Akt pathway.^[1] ^[2] [SLB2_DEIAC] Agglucetin specifically causes platelet aggregation and surface exposure of integrin alpha-IIb/beta-3 with a GPIb-(GP1BA-) dependent manner in washed platelets. It binds to human platelets in a saturable manner, and its binding is specifically blocked by anti-GP Ib mAb. It regulates endothelial cell survival and promotes angiogenesis by activating integrin alpha-v/beta-3 signaling through FAK/phosphatidylinositol 3-kinase (PI3K)/Akt pathway.^[3] ^[4]

Publication Abstract from PubMed

Agkisacucetin is a snake C-type lectin isolated from the venom of Agkistrodon acutus (A. acutus). It binds specifically to the platelet glycoprotein (GP) Ib and prevents the von Willebrand factor (VWF) accessing it. We determined the crystal structure of agkisacucetin to 1.9A resolution. The structure of agkisacucetin has an (alphabeta) fold similar to another GPIb-binding protein, flavocetin-A, but lacks the C-terminal cysteine in the beta-subunit, does not form (betaalpha)(4) tetramers, and does not cluster GPIbs, like flavocetin-A.

Crystal structure of agkisacucetin, a Gpib-binding snake C-type lectin that inhibits platelet adhesion and aggregation.,Gao Y, Ge H, Chen H, Li H, Liu Y, Chen L, Li X, Liu J, Niu L, Teng M Proteins. 2012 Jun;80(6):1707-11. doi: 10.1002/prot.24060. Epub 2012 Mar 23. PMID:22447656^[5]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Wang WJ, Huang TF. A novel tetrameric venom protein, agglucetin from Agkistrodon acutus, acts as a glycoprotein Ib agonist. Thromb Haemost. 2001 Oct;86(4):1077-86. PMID:11686327
↑ Wang WJ. Agglucetin, a tetrameric C-type lectin-like venom protein, regulates endothelial cell survival and promotes angiogenesis by activating integrin alphavbeta3 signaling. Biochem Biophys Res Commun. 2008 May 2;369(2):753-60. doi:, 10.1016/j.bbrc.2008.02.091. Epub 2008 Feb 27. PMID:18312855 doi:http://dx.doi.org/10.1016/j.bbrc.2008.02.091
↑ Wang WJ, Huang TF. A novel tetrameric venom protein, agglucetin from Agkistrodon acutus, acts as a glycoprotein Ib agonist. Thromb Haemost. 2001 Oct;86(4):1077-86. PMID:11686327
↑ Wang WJ. Agglucetin, a tetrameric C-type lectin-like venom protein, regulates endothelial cell survival and promotes angiogenesis by activating integrin alphavbeta3 signaling. Biochem Biophys Res Commun. 2008 May 2;369(2):753-60. doi:, 10.1016/j.bbrc.2008.02.091. Epub 2008 Feb 27. PMID:18312855 doi:http://dx.doi.org/10.1016/j.bbrc.2008.02.091
↑ Gao Y, Ge H, Chen H, Li H, Liu Y, Chen L, Li X, Liu J, Niu L, Teng M. Crystal structure of agkisacucetin, a Gpib-binding snake C-type lectin that inhibits platelet adhesion and aggregation. Proteins. 2012 Feb 22. doi: 10.1002/prot.24060. PMID:22447656 doi:10.1002/prot.24060

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OCA

[1] Wang WJ, Huang TF. A novel tetrameric venom protein, agglucetin from Agkistrodon acutus, acts as a glycoprotein Ib agonist. Thromb Haemost. 2001 Oct;86(4):1077-86. PMID:11686327

[2] Wang WJ. Agglucetin, a tetrameric C-type lectin-like venom protein, regulates endothelial cell survival and promotes angiogenesis by activating integrin alphavbeta3 signaling. Biochem Biophys Res Commun. 2008 May 2;369(2):753-60. doi:, 10.1016/j.bbrc.2008.02.091. Epub 2008 Feb 27. PMID:18312855 doi:http://dx.doi.org/10.1016/j.bbrc.2008.02.091

[3] Wang WJ, Huang TF. A novel tetrameric venom protein, agglucetin from Agkistrodon acutus, acts as a glycoprotein Ib agonist. Thromb Haemost. 2001 Oct;86(4):1077-86. PMID:11686327

[4] Wang WJ. Agglucetin, a tetrameric C-type lectin-like venom protein, regulates endothelial cell survival and promotes angiogenesis by activating integrin alphavbeta3 signaling. Biochem Biophys Res Commun. 2008 May 2;369(2):753-60. doi:, 10.1016/j.bbrc.2008.02.091. Epub 2008 Feb 27. PMID:18312855 doi:http://dx.doi.org/10.1016/j.bbrc.2008.02.091

[5] Gao Y, Ge H, Chen H, Li H, Liu Y, Chen L, Li X, Liu J, Niu L, Teng M. Crystal structure of agkisacucetin, a Gpib-binding snake C-type lectin that inhibits platelet adhesion and aggregation. Proteins. 2012 Feb 22. doi: 10.1002/prot.24060. PMID:22447656 doi:10.1002/prot.24060

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