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 > 586 Saint James Walk > Marietta GA 30067-7165 > 404-788-1216 (C)<- leave message > 989-348-4796 (P)<- emergency only > [EMAIL PROTECTED] > Note: If I am asking for free stuff, I normally use for hobby/non-profit > information but may use in investment forums, public and private. > Please indicate any concerns if applicable. > Note: Hotmail is possibly blocking my mom's entire > ISP - try me on [EMAIL PROTECTED] if no reply > here. Thanks. > > > > Date: Mon, 31 Mar 2008 10:21:18 +0200 > > From: [EMAIL PROTECTED] > > To: [email protected] > > 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 > > [email protected] > > http://www.bioinformatics.org/mailman/listinfo/bbb > > _________________________________________________________________ > Use video conversation to talk face-to-face with Windows Live Messenger. > http://www.windowslive.com/messenger/connect_your_way.html?ocid=TXT_TAGLM_WL_Refresh_messenger_video_042008 > _______________________________________________ > BBB mailing list > [email protected] > http://www.bioinformatics.org/mailman/listinfo/bbb > _______________________________________________ BBB mailing list [email protected] http://www.bioinformatics.org/mailman/listinfo/bbb
