Abstract:
:Polypeptide toxins isolated from the venom of cone snails, known as μ-conotoxins, block voltage-gated sodium channels by physically occluding the ion-conducting pathway. Using molecular dynamics, we show that one subtype of μ-conotoxins, PIIIA, effectively blocks the bacterial voltage-gated sodium channel Na(V)Ab, whose crystal structure has recently been elucidated. The spherically shaped toxin, carrying a net charge of +6 e with six basic residues protruding from its surface, is attracted by the negatively charged residues on the vestibular wall and the selectivity filter of the channel. The side chain of each of these six arginine and lysine residues can wedge into the selectivity filter, whereas the side chains of other basic residues form electrostatic complexes with two acidic residues on the channel. We construct the profile of potential of mean force for the unbinding of PIIIA from the channel, and predict that PIIIA blocks the bacterial sodium channel with subnanomolar affinity.
journal_name
Biophys Jjournal_title
Biophysical journalauthors
Chen R,Chung SHdoi
10.1016/j.bpj.2011.12.041subject
Has Abstractpub_date
2012-02-08 00:00:00pages
483-8issue
3eissn
0006-3495issn
1542-0086pii
S0006-3495(11)05472-5journal_volume
102pub_type
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