Research into toxins points to development of better medicines

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Research into toxins points to development of better medicines

http://www.news-medical.net/?id=17545

An international research team determines how toxins attach to

potassium channels - and change their internal structure

Researchers from the Max Planck Institite for Biophysical Chemistry

and other German and French colleagues have combined magnetic

resonance spectroscopy (solid-state NMR) with special protein

synthesis procedures to uncover how potassium channels and toxins

combine and change in structure. This work could make it possible to

develop medications for high blood pressure and many other diseases

connected to potassium channel failure (Nature, April 13, 2006).

Our body's cells have membranes, and " ion channels " are embedded in

them. Ion channels are special proteins which let only certain ions

through the membrane. The channels build an electro-chemical

gradient, allowing nerve and heart muscle cell signals to pass. The

nerve or heart muscle cell is excited, and the ion channel structure

changes, developing pores which let the ions through. Different

channels are open to different specific ions; for example, potassium

channels only allow potassium ions through. Poisonous animals use

very specific toxins to target channels; the toxins block the

channels and make it impossible for electric signals to move through

the membrane - often killing the cell.

These kind of interactions had not been well investigated at a

structural level - even though scientists had made great strides

studying ion channels, using x-ray crystallography. Scientists from

the Max Planck Institute for Biophysical Chemistry in Gvttingen,

working together with researchers from the Institute for Neural

Signal Processing in Hamburg and French colleagues from the

University of Marseille, combined a new method of solid-state NMR

with particular protein synthesis procedures and looked at the

example of poison from the north African scorpion Androctonus

mauretanicus mauretanicus, to determine how bacterial potassium

channels interact with toxins at an atomic level.

The researchers first examined the electrophysiological

characteristics of the " poisoned " channel protein. The

scientists " spin-marked " some of them and investigated them with

solid-state NMR. Spin-marked proteins contain carbon and nitrogen

atoms with an intrinsic magentic moment (spin) which strengthens the

NMR's signals. Looking at spectroscopic data before and after the

toxin affected the channel, it turned out that the poison attaches to

a particular area of the channel - the pore region - and changes the

area's structure. The poison is thus only effective when it

recognises a particular amino acid sequence in the ion channel. It is

also important how intrinsically flexible the binding partner is; for

a strong interaction to take place, the molecules of both partners

have to be able to change their structures.

Applying these new spectroscopic methods, scientists are now better

understanding the pharmacology and physiology of potassium channels.

This could lead to better, more specific medications.

http://www.mpg.de