[BiO BB] TopMatch protein structure alignment and superposition web service

[Markus Wiederstein]

Hi Mike,

thanks for pointing to this interesting test case.

Indeed, the structural similarity of dehydrosqualene synthase (PDB codes: 2zco, 2zcp, 2zcq, 2zcr, 2czs) and humane squalene synthase (PDB codes 1ezf) is striking in the view of their low sequence identity. TopMatch-web yields an RMS of 3.5A and a sequence identity of 11% if the respective chains A are compared.

Talking about finding such similarities: one tool that is really helpful for this task is the qCOPS web service (some advertising again ;-) at
http://navi.services.came.sbg.ac.at/bin/qCOPS.html

For each protein deposited in PDB, you can easily explore its structural neighborhood and visualize structural similarities with TopMatch.
If you try with the example you mentioned, you find the dehydrosqualene synthase structures assigned to be similar to 1ezf.

For further information on qCOPS, see 
Sippl et al.
A Discrete View on Fold Space 
Bioinformatics, 24, pp. 870-871 (2008)
(Open Access: http://bioinformatics.oxfordjournals.org/cgi/reprint/btn020?ijkey=7zgnEsdKQIEfrN7&keytype=ref)

Best regards,
-Markus

On Die, 01 Apr 2008, Mike Marchywka wrote:

> 
> If you use this kind of tool, you may be interested in this relevant test case from Nature today.
> Could you devise a strategy or find a tool that could have found this similarity?
> I'm not sure what they mean by "earlier studies" but I assume it wasn't some guy BLAST'ing 
> a 3D databse. You need to register but it is free,
> 
> http://www.nature.com/nrd/journal/v7/n4/full/nrd2554.html
> 
> 
> "
> 
> An important virulence factor in S. aureus is the vivid golden carotenoid pigment staphyloxanthin, which acts as an antioxidant to evade attack by reactive oxygen species from the host immune system. Inhibition of staphyloxanthin biosynthesis is therefore an attractive potential therapeutic strategy to block bacterial infection.
> 
> Interestingly, earlier studies have noted that the process of staphyloxanthin production is strikingly similar to that of human cholesterol synthesis. Here, using X-ray crystallography, the authors analysed the structure of an essential enzyme involved in the first crucial step of staphyloxanthin biosynthesis: dehydrosqualene synthase (CrtM). They cloned and purified CrtM from S. aureus and revealed that despite only modest sequence homology, it had close structural similarity to human squalene synthase (SQS). This led to the hypothesis that inhibitors of SQS that had already been developed as cholesterol-lowering drugs might also be active against CrtM.
> 
> "
> 
> 
> 
> Mike Marchywka
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> 
> 
> > Date: Mon, 31 Mar 2008 10:21:18 +0200
> > From: markii at came.sbg.ac.at
> > To: bbb at bioinformatics.org
> > Subject: [BiO BB] TopMatch protein structure alignment and superposition web service
> >
> > We announce the release of TopMatch-web, a public web service for the alignment and superposition of protein structures and the instant
> > +visualization of structural similiarities.
> >
> > We believe that TopMatch is an exceptionally effective, accurate, and enjoyable program for the investigation of protein structure similarities.
> >
> > For further information and instructive examples see
> > Sippl & Wiederstein (2008)
> > A Note on Difficult Structure Alignment Problems.
> > Bioinformatics 24, pp. 426-427
> >
> > TopMatch-web is available as a public web service at http://topmatch.services.came.sbg.ac.at.
> >
> > Enjoy!
> >
> > The TopMatch Team
> > Center of Applied Molecular Engineering
> > University of Salzburg
> > Austria
> >
> > _______________________________________________
> > BBB mailing list
> > BBB at bioinformatics.org
> > http://www.bioinformatics.org/mailman/listinfo/bbb
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