Modification of substrate inhibition of synaptosomal acetylcholinesterase by cardiotoxins.
Different types of cardiotoxin (I-V and n) were isolated and purified from the venom of the Taiwan cobra (Naja naja atra). The effects of these cardiotoxins were studied on membrane-bound acetylcholinesterase, which was isolated from a sheep's brain cortex. The results showed that cardiotoxins I-III, V, and n activated the enzyme by modification of substrate inhibition, but cardiotoxin IV's reaction was different. The inhibition and activation of acetylcholinesterase were linked to the functions of the hydrophobicity index, presence of a cationic cluster, and the accessible arginine residue. Our results indicate that Cardiotoxins have neither a cationic cluster nor an arginine residue in their surface area of loop I; therefore, in contrast to fasciculin, cardiotoxins are attached by loop II to the peripheral site of the enzyme. As a result, fasciculin seems to stabilize nonfunctional conformation, but cardiotoxins seem to stabilize the functional conformation of the enzyme. Based on our experimental and theoretical findings, similar secondary and tertiary structures of cardiotoxins and fasciculin seem to have an opposite function once they interact with acetylcholinesterase.
Ranaei-Siadat
Seyed-Omid
SO
Institute of Biotechnology and Biophysics, University of Tehran, Tehran, Iran.
Riazi
Gholam-Hosein
GH
Sadeghi
Mehdi
M
Chang
Long-Sen
LS
Lin
Shinne-Ren
SR
Eghtesadi-Araghi
Peyman
P
Hakimelahi
Gholam Hossein
GH
Moosavi-Movahedi
Ali Akbar
AA
D000110:Acetylcholinesterase / Q000737:chemistry / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D001923:Brain Chemistry; D002540:Cerebral Cortex / Q000201:enzymology; D004179:Cobra Cardiotoxin Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004546:Elapid Venoms / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017815:Elapidae; D004789:Enzyme Activation; D008969:Molecular Sequence Data; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D012756:Sheep; D013574:Synaptosomes / Q000201:enzymology*
D004179:Cobra Cardiotoxin Proteins; D004546:Elapid Venoms; C044937:fasciculin; D000110:Acetylcholinesterase