[tt] Fwd: [Hplusroadmap] Bacteria with 'brain' proteins?

[Bryan Bishop]

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Subject: [Hplusroadmap] Bacteria with 'brain' proteins?
Date: Wednesday 25 June 2008
From: "Dan Bolser" <dan.bolser at gmail.com>
To: hplusroadmap at heybryan.org

Just for your interest...
http://www.rcsb.org/pdb/explore/pubmed.do?structureId=2A65

Article Title   	
Crystal structure of a bacterial homologue of Na+/Cl--dependent
neurotransmitter transporters.

Abstract
Na+/Cl--dependent transporters terminate synaptic transmission by
using electrochemical gradients to drive the uptake of
neurotransmitters, including the biogenic amines, from the synapse to
the cytoplasm of neurons and glia. These transporters are the targets
of therapeutic and illicit compounds, and their dysfunction has been
implicated in multiple diseases of the nervous system. Here we present
the crystal structure of a bacterial homologue of these transporters
from Aquifex aeolicus, in complex with its substrate, leucine, and two
sodium ions. The protein core consists of the first ten of twelve
transmembrane segments, with segments 1-5 related to 6-10 by a
pseudo-two-fold axis in the membrane plane. Leucine and the sodium
ions are bound within the protein core, halfway across the membrane
bilayer, in an occluded site devoid of water. The leucine and ion
binding sites are defined by partially unwound transmembrane helices,
with main-chain atoms and helix dipoles having key roles in substrate
and ion binding. The structure reveals the architecture of this
important class of transporter, illuminates the determinants of
substrate binding and ion selectivity, and defines the external and
internal gates.

Dan.
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