Linked Life Data

10727107

Source:http://linkedlifedata.com/resource/pubmed/id/10727107

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2000-4-28
pubmed:abstractText
Maurotoxin (MTX) is a 34-amino acid polypeptide cross-linked by four disulfide bridges that has been isolated from the venom of the scorpion Scorpio maurus palmatus and characterized. Maurotoxin competed with radiolabeled apamin and kaliotoxin for binding to rat brain synaptosomes and blocked K+ currents from Kv1 channel subtypes expressed in Xenopus oocytes. Structural characterization of the synthetic toxin identified half-cystine pairings at Cys3-Cys24, Cys9-Cys29, Cys13-Cys19 and Cys31-Cys34 This disulfide bridge pattern is unique among known scorpion toxins, particularly the existence of a C-terminal '14-membered disulfide ring' (i.e. cyclic domain 31-34), We therefore studied structure-activity relationships by investigating the structure and pharmacological properties of synthetic MTX peptides either modified at the C-terminus ¿i.e. MTX(1-29), [Abu31,34]-MTX and [Cys31,34, Tyr32]D-MTX) or mimicking the cyclic C-terminal domain [i.e. MTX(31-34)]. Unexpectedly, the absence of a disulfide bridge Cys31-Cys34 in [Abu 31,34]-MTX and MTX(1-29) resulted in MTX-unrelated half-cystine pairings of the three remaining disulfide bridges for the two analogs, which is likely to be responsible for their inactivity against Kv1 channel subtypes. Cyclic MTX(31-34) was also biologically inactive. [Cys31,34, Tyr32]D-MTX, which had a 'native', MTX-related, disulfide bridge organization, but a D-residue-induced reorientation of the C-terminal disulfide bridge, was potent at blocking the Kv1.1 channel. This peptide-induced Kv1.1 blockage was voltage-dependent (a property not observed for MTX), maximal in the low depolarization range and associated with on-rate changes in ligand binding. Thus, the cyclic C-terminal domain of MTX seems to be crucial for recognition of Kv1.3, and to a lesser extent, Kv1.2 channels and it may contribute to the stabilization and strength of the interaction between the toxin and the Kv1.1 channel.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1397-002X
pubmed:author
pubmed:issnType
Print
pubmed:volume
55
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
246-54
pubmed:dateRevised
2005-11-17
pubmed:meshHeading
pubmed-meshheading:10727107-Amino Acid Sequence, pubmed-meshheading:10727107-Animals, pubmed-meshheading:10727107-Apamin, pubmed-meshheading:10727107-Binding, Competitive, pubmed-meshheading:10727107-Brain, pubmed-meshheading:10727107-Chromatography, High Pressure Liquid, pubmed-meshheading:10727107-Disulfides, pubmed-meshheading:10727107-Electrophysiology, pubmed-meshheading:10727107-Kv1.1 Potassium Channel, pubmed-meshheading:10727107-Molecular Sequence Data, pubmed-meshheading:10727107-Neurotoxins, pubmed-meshheading:10727107-Oocytes, pubmed-meshheading:10727107-Peptide Fragments, pubmed-meshheading:10727107-Peptides, Cyclic, pubmed-meshheading:10727107-Potassium Channels, pubmed-meshheading:10727107-Potassium Channels, Voltage-Gated, pubmed-meshheading:10727107-Rats, pubmed-meshheading:10727107-Scorpion Venoms, pubmed-meshheading:10727107-Xenopus
pubmed:year
2000
pubmed:articleTitle
Maurotoxin and the Kv1.1 channel: voltage-dependent binding upon enantiomerization of the scorpion toxin disulfide bridge Cys31-Cys34.
pubmed:affiliation
Laboratoire de Biochimie, CNRS UMR 6560, IFR Jean Roche, Faculté de Médecine Nord, Marseille, France. lecomte.c@jean-roche.univ-mrs.fr
pubmed:publicationType
Journal Article