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Crystal Structure of Fasciculin 2 from Green Mamba Snake Venom: Evidence for Unusual Loop Flexibility
Structural highlights
Function3SE2_DENAN Interferes with neuromuscular transmission by inhibiting the enzyme acetylcholinesterase (AChE) present at the neuromuscular junction. It selectively binds and inhibits with a 1:1 stoichiometry the mammalian and electric fish AChE at picomolar concentrations. It is highly specific for the peripheral site of AChE and blocks the entry of acetylcholine into the active site of the enzyme (through the Met-33 residue), thereby preventing its breakdown. It has been called fasciculin since after injection into mice it causes severe, generalized and long-lasting (5-7 hours) fasciculations.[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 PubMedThe crystal structure of the snake toxin fasciculin 2, a potent acetylcholinesterase inhibitor from the venom of the green mamba (Dendroaspis angusticeps), has been determined by the molecular-replacement method, using the fasciculin 1 model and refined to 2.0 A resolution. The introduction of an overall anisotropic temperature factor improved significantly the quality of the electron-density map. It suggests, as it was also indicated by the packing, that the thermal motion along the unique axis direction is less pronounced than on the (ab) plane. The final crystallographic R factor is 0.188 for a model having r.m.s. deviations from ideality of 0.016 A for bond lengths and 2.01 degrees for bond angles. As fasciculin 1, fasciculin 2 belongs to the three-finger class of Elapidae toxins, a structural group that also contains the alpha-neurotoxins and the cardiotoxins. Although the two fasciculins have, overall, closely related structures, the conformation of loop I differs appreciably in the two molecules. The presence of detergent in crystallization medium in the case of fasciculin 2 appears to be responsible for the displacement of the loop containing Thr9. This conformational change also results in the formation of a crystallographic dimer that displays extensive intermolecular interactions. Structure of fasciculin 2 from green mamba snake venom: evidence for unusual loop flexibility.,le Du MH, Housset D, Marchot P, Bougis PE, Navaza J, Fontecilla-Camps JC Acta Crystallogr D Biol Crystallogr. 1996 Jan 1;52(Pt 1):87-92. PMID:15299729[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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