Structural highlights
Function
[3NO5I_BUNMU] Exhibits M2 muscarinic acetylcholine receptor (CHRM2)-blocking activity, but has a weak binding activity toward nicotinic AChR. Moreover, it inhibits collagen-induced platelet aggregation.[1]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Gamma-bungarotoxin, a snake venom protein isolated from Bungarus multicinctus, contains 68 amino acids, including 10 cysteine residues and a TAVRGDGP sequence at positions 30-37. The solution structure of gamma-bungarotoxin has been determined by nuclear magnetic resonance (NMR) spectroscopy. The structure is similar to that of the short-chain neurotoxins that contain three loops extending from a disulfide-bridged core. The tripeptide Arg-Gly-Asp (RGD) sequence is located at the apex of the flexible loop and is similar to that of other RGD-containing proteins. However, gamma-bungarotoxin only inhibits platelet aggregations with an IC50 of 34 microM. To understand its weak activity in inhibiting platelet aggregation, we mutated the RGD loop sequences of rhodostomin, a potent platelet aggregation inhibitor, from RIPRGDMP to TAVRGDGP, resulting in a 196-fold decrease in activity. In addition, the average Calpha-to-Calpha distance between R33 and G36 of gamma-bungarotoxin is 6.02 A, i.e., shorter than that of other RGD-containing proteins that range from 6.55 to 7.46 A. These results suggested that the amino acid residues flanking the RGD motif might control the width of the RGD loop. This structural difference may be responsible for its decrease in platelet aggregation inhibition compared with other RGD-containing proteins.
Solution structure of gamma-bungarotoxin: the functional significance of amino acid residues flanking the RGD motif in integrin binding.,Shiu JH, Chen CY, Chang LS, Chen YC, Chen YC, Lo YH, Liu YC, Chuang WJ Proteins. 2004 Dec 1;57(4):839-49. PMID:15390258[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Chang LS, Chung C, Wu BN, Yang CC. Characterization and gene organization of Taiwan banded krait (Bungarus multicinctus) gamma-bungarotoxin. J Protein Chem. 2002 May;21(4):223-9. PMID:12168693
- ↑ Shiu JH, Chen CY, Chang LS, Chen YC, Chen YC, Lo YH, Liu YC, Chuang WJ. Solution structure of gamma-bungarotoxin: the functional significance of amino acid residues flanking the RGD motif in integrin binding. Proteins. 2004 Dec 1;57(4):839-49. PMID:15390258 doi:10.1002/prot.20269
