Question: Mutation impact on DNA binding
0
gravatar for ciemanek
18 months ago by
ciemanek110
The Netherlands/Amsterdam
ciemanek110 wrote:

Hi all,

I am very new in the topic of proteins modelling and I don really know where to start with. We are working on MCM3 protein which is a part of MCM2-7 complex. We identified a mutation of interest following into the ATP binding domain. Therefore, we want to check whether this mutation introduces changes into ATP binding or complex formation with other proteins. I found a structure in PDB of a MCM2-7 complex which is coming from S. cerevisiae and I wonder how should I proceed with further analysis. If anyone could list the basic steps which i should take and parameters that are informative for binding and complex formation, that would be highly appreciated. Maybe there are some tutorials covering the issue? I imagine that modelling mutation impact on binding is quite common task however I only found instructions regarding homology modelling itself and I don't know how to apply it for my question.

All the best, Agata

ADD COMMENTlink modified 17 months ago by Biostar ♦♦ 20 • written 18 months ago by ciemanek110
3

While all this sounds simple it can be challenging to do and correct interpretation of results is extremely important as well. If possible see if you can find a local structural bioinformatics expert willing to collaborate. This can save you time and may prove mutually beneficial.

ADD REPLYlink written 18 months ago by genomax68k
1

There are a lot of articles about the protein. It’s a very interesting one, thank you!

See this paper:

https://www.ncbi.nlm.nih.gov/pubmed/19910535

Proc Natl Acad Sci U S A. 2009 Dec 1;106(48):20240-5. doi: 10.1073/pnas.0911500106. Epub 2009 Nov 12.

A double-hexameric MCM2-7 complex is loaded onto origin DNA during licensing of eukaryotic DNA replication. Evrin C1, Clarke P, Zech J, Lurz R, Sun J, Uhle S, Li H, Stillman B, Speck C. It has more than 100 citations. They may be useful.

http://www.tandfonline.com/doi/abs/10.1080/10409238.2016.1274717

Mechanisms and regulation of DNA replication initiation in eukaryotes.

Matthew W. Parker, Michael R. Botchan & James M. Berger Pages 107-144 | Received 17 Oct 2016, Accepted 16 Dec 2016, Published online: 17 Jan 2017

https://doi.org/10.1080/10409238.2016.1274717

There should be some models here as well.

ADD REPLYlink written 18 months ago by natasha.sernova3.5k
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