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Web Site Proteins Never Change a Winning Horse.

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Angewandte
Web Sites
Chemie
Proteins:
Never Change a Winning Horse
Now that the genomes of various organisms have been deciphered, the focus in
life sciences shifts back to proteins, the
true carriers of cellular functions. Our
knowledge on proteins accumulates rapidly. Every day new sequences and highresolution 3D structures are added to
the databases. However, the knowledge
on the relationship between sequence,
structure, and function lags behind. But
in many cases, we depend on just that
knowledge if we wish to exploit the
available sequence information. To explore the biological function experimentally, for example by mutating single
amino acid residues one by one, is often
tedious and time consuming. So tools
that help us to address this issue are
most welcome.
ConSurf is such a tool. It was crafted
by bioinformatics researchers from Israel and the United States and sets out
to identify functional regions of proteins. ConSurf is short for conservation
and surface, and the name points to its
basic premise: Features that are particularly important will change only slowly
over time. Therefore ConSurf examines
to which extent the single amino acid
residues in a sequence have been conserved in the course of evolution. Starting from a known protein structure, a
colored representation is generated
which shows the degree of amino acid
conservation in a graded color code
(Figure 1).
ConSurf mainly uses well established protein analysis algorithms, but the
intelligent combination of these in a
single user surface and the convincing
Angew. Chem. Int. Ed. 2003, 42, 1193
graphical output make it a valuable tool
on its own.
In ConSurf.s “Overview” chapter,
the detailed methodology is explained
clearly and step by step: The known
protein structure has to be provided in
PDB format. First, a database search for
similar sequences is carried out (PSI
Blast) and a multiple alignment of these
is generated (ClustalW). Then, a phylogenetic tree is built and the degree of
conservation is estimated from that tree.
One can choose a method, for example
Rate4Site, an improved variant of the
maximal-likelihood method.[1] The conservation scores obtained in this way are
projected onto the protein surface using
a color scheme with nine color grades
from turquoise to burgundy and the
structure is visualized online (Protein
Explorer). The degree of conservation
then can be observed directly looking at
the 3D structure.
But we don.t have to care for these
details. ConSurf is ”user-friendly and
fully automatic,” Nir Ben-Tal, one of the
ConSurf authors emphasizes. Database
accession number in, color image out—
it.s as easy as that.
But one thing ConSurf can.t tell us
yet: The real meaning of such a result.
The possible reasons why a particular
region of a protein is conserved more
than the rest are manifold: It may be the
catalytic center or an important contact
surface for partner proteins, but it may
as well be crucial for the formation of
the correct global fold. And be aware
that proteins exist in which everything is
well conserved except the decisive binding region, such as immunoglobulins.
Suggest a web site or submit a review:
angewandte@wiley-vch.de
So we come full circle: ConSurf is a
useful tool. It can put us on the right
track, but the interpretation of the
suggestive pictures that it projects onto
our computer screens is still left to the
researchers. intelligence and imagination.
Christoph Weise
Institute of Chemistry,
Freie Universitt Berlin
(Germany)
[1] T. Pupko, R. E. Bell, I. Mayrose, F. Glaser,
N. Ben-Tal, Bioinformatics 2002, 18, 71.
Figure 1. The potassium channel according to
ConSurf—the amino acids at the ion channel are
highly conserved (burgundy); yellow: the permeating ions.
( 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
For more information visit
http://consurf.tau.ac.il
or contact
bental@ashtoret.tau.ac.il
http://www.interscience.wiley.com/alerts
1433-7851/03/4211-1193 $ 20.00+.50/0
1193
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