[qw098]

Hi Guys,

I was wondering how I can tell the difference between a Major and Minor groove binder (on DNA)? What do they have different in terms of structure and properties?

I tried googling it... but nothing came up!

Thanks!

[Babcock_Hall]

The majority of proteins (and also drugs) bind in the major groove, but a small percentage bind to the minor groove.  Are you interested in proteins that bind to DNA or drugs that bind to DNA.

[qw098]

I am looking for more so the general structure of a major groove binder or minor groove binder, be it a drug or protein.

I imagine the drug or protein must have structural thematic similarities if lets say drug A and protein A both were major groove binders. Same would hold true if both were minor groove binders I think.

[Yggdrasil]

As with many things in biology, evolution has come across many different solutions to the same problem, so there is no one solution that nature uses to recognize DNA.  There are various structural domains that function primarily to recognize the major or minor groove of DNA (for major groove-binders, see for example the basic helix-loop-helix domain, or a zinc finger domain).  One common theme for major groove binders, however, is insertion of an alpha helix along the major groove of the DNA (although I'm sure there are examples where the interaction does not involve an alpha helix).

For small molecules, there are various classes of molecules that scientists have designed to specifically recognize DNA.  For an example of major groove binders, see the work on polyamides by Peter Dervan at Caltech.

[Babcock_Hall]

R. Rohs et al., “Origins of Specificity in Protein-DNA Recognition”  Annual Review of Biochemistry (2010), 79: 233-69.
Page 253 discusses the use of arginines to bind in the minor groove.  There is also some discussion on page 251 and possibly elsewhere.  The second edition of “The Organic Chemistry of Drug Design and Drug Action,” by Richard Silverman has a discussion of groove binding on pages 345-346.  I will quote a short portion:  “Minor groove binding molecules generally have aromatic rings connected by single bonds that allow for torsional rotation in order to fit into the helical curvature of the groove with displacement of water molecules.”