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PDB:1MAH

Protein Name

Complex of acetylcholinesterase and fasciculin 2

Species

Mus musculus (house mouse) / Dendroaspis angusticeps (eastern green mamba)

Biological Context

When we touch a hot material by hand, we immediately make an action, withdrawing the hand. This reaction is done very quickly by using synaptic signaling, one of the ways to transmit information from cell to cell. Other ways (contact-dependent signaling, paracrine signaling and endocrine signaling) are done much slowly. Nerve cells, or neurons, which typically extend long process (axons) that enables them to contact target cells far away. The signals are transmitted electrically along their axons and release neurotransmitters at synapses. Usually, only a target cell that is in synaptic communication with a nerve cell is exposed to the neurotransmitter released from the nerve terminal. Acetylcolin is one of the major neurotransmitters. For maintaining a quick response, after neurotransmitters have been secreted, they are rapidly removed; it is either destroyed by specific enzymes in the synaptic cleft or taken up by the nerve terminal that released them or by surrounding glial cells. The structure shown here is a complex of acetylcholinesterase (AChE), an enzyme that breaks down unused acetylcholin in the synaptic cleft for preparing the next nerve impulse, with its inhibitor, fasciculin. Fasciculins are 61 amino acids peptide isolated from mamba venoms, and are the only known peptide AChE inhibitor. They are highly selective in that they only inhibit mammalian and electric eel AChE. The AChE molecule has the alpha beta hydrase fold and consists of the same 12-stranded central-mixed beta sheet surrounded by 14 alpha helices. Three loops of fasciculin emerging from a dense core containing disulfide bridges, form a slightly concave flat disk, and that fits into an elongated cavity at the surface of AChE. The three loops are anchored to AChE separately, resulting a particularly well-ordered molecule of bound fasciculin. Loop 2 of fasciculin contains a several hydrophobic residues that interact with the peripheral anionic site of the AChE and occlude the entrance of the gorge for substrate acetylcholin. Loop 1 fits in a crevice near the lip of the gorge to maximize the surface area for helping the contact of loop 3 at the gorge entry. Loop 3 also may contribute to stabilizing the position in loop 2.

Structure Description

1mah1mah_x1mah_y

The structure shown here is a complex of acetylcholinesterase (AChE), an enzyme that breaks down unused acetylcholin in the synaptic cleft for preparing the next nerve impulse, with its inhibitor, fasciculin. Fasciculins are 61 amino acids peptide isolated from mamba venoms, and are the only known peptide AChE inhibitor. They are highly selective in that they only inhibit mammalian and electric eel AChE. The AChE molecule has the alpha beta hydrase fold and consists of the same 12-stranded central-mixed beta sheet surrounded by 14 alpha helices. Three loops of fasciculin emerging from a dense core containing disulfide bridges, form a slightly concave flat disk, and that fits into an elongated cavity at the surface of AChE. The three loops are anchored to AChE separately, resulting a particularly well-ordered molecule of bound fasciculin. Loop 2 of fasciculin contains a several hydrophobic residues that interact with the peripheral anionic site of the AChE and occlude the entrance of the gorge for substrate acetylcholin. Loop 1 fits in a crevice near the lip of the gorge to maximize the surface area for helping the contact of loop 3 at the gorge entry. Loop 3 also may contribute to stabilizing the position in loop 2.

Protein Data Bank (PDB)

References

Source

  • Bourne, Y. Taylor, P. Marchot, P.; "Acetylcholinesterase inhibition by fasciculin: crystal structure of the complex."; Cell; (1995) 83:503-512 PubMed:8521480.

Others

author: Sachiyo Nomura


Japanese version:PDB:1MAH