The week in Structures – 1st May 2013 #PDB

May 1, 2013

The first in a (hopefully) weekly series of reviews of interesting structures in latest PDB release**.

High-resolution* Cryo-EM models of Human and Drosophilia Ribosomes!

Proteins are the major molecular players in life as we know it – they are the chemists, the engineers, the messengers and the defenders of life. They make new chemical compounds that we need, they break old compounds down so that we might re-use them – they transmit messages between different cells and tissues and help identify invading pathogens. In short – proteins do pretty much everything, and as such are the subject of intense study and scrutiny.

What better subject for the first of my PDB release highlight posts, than the Ribosome – a vast (at least at a molecular level) and ancient molecular machines that are responsible for the synthesis of proteins in our cells. The (perhaps outdated) “central dogma” of biology is that DNA is transcribed to mRNA, which is translated into protein, and the proteins then go and do everything. Anger et al have released 5Å resolution Cryo-EM-derived models of human and drosophila (Fruit Fly) ribosomes – they are so vast that they have to be split across several PDB files each…

Human (3J3A, 3J3D, 3J3B, 3J3F)

Drosophila (3J38, 3J3C, 3J39, 3J3E)

We're gonna need a bigger boat.

… and so complex as to defy creation of a clear and crisp picture.

The Paper concerning these is due to be published in Nature, but is not available at the time of writing (EDIT – Now it is – here (£)). Presumably, along with the methods  employed in what must be a massive modelling task, there will be some discussion of the differences between these two eukaryotic ribosomes, and the prokaryotic ribosome structures that were the subject of the 2009 Nobel Prize for Chemistry.

Other highlights in this weeks crop of 287 PDB releases include yet more BACE-inhibitor complexes (potential lead compounds for Altzheimer‘s treatments) and CDK2 and CDK8 -inhibitor complexes, which may be lead to novel anti-cancer therapies.

*ok – 5Å might not be great for crystallography, but for our Cryo-EM-based friends, this is pushing the limits and is clearly the result of a great deal of hard work and a massive amount of particle picking.

** The PDB is the “Protein Data Bank” – all structures of proteins/DNA and related molecules are deposited into the PDB and then made available to everyone (for free) prior to or at the time of publication of the paper that describes the work pertaining to the structure. The PDB issues new releases every Wednesday morning (UK time).

Definition: “Sequence Gazing”

February 3, 2013

ImageSequence gazing (vb):

A technique similar to meditation, often practised by molecular biologists and biochemists. To gaze intently at amino acid and DNA sequences, and multiple alignments thereof, until either “the answer” or a testable hypothesis presents itself.