2005-A Structural Summary

This post is highly technical, so if you haven't a clue what I'm saying here don't worry. I will return to my previous style after this. Continuing the year-end theme, I just finished reading Science Magazine's top discoveries of 2005 . As I view and work with protein structures regularly, I thought, for any others who are into structural biology, that I'd give my opinion on the most exciting biomolecular structures released at the RCSB Protein Data Bank (PDB) in 2005. I understand this is going to be a rather biased list, as it is based on my personal opinion only, and I am sure I am not aware of many structures deposited in the PDB in the last year.

First on my list would have to be a structure solved by a professor here at Cal whose lab I worked in during Fall 2004, Jamie Cate. In what is surely the largest nucleic acid structure ever solved at near-atomic resolution, he and members of his lab (me not included) have determined the 3.46 Angstrom crystal structure of the entire E. coli ribosome (PDB IDs 2AVY, 2AW4, 2AW7, and 2AWB), offering the first glimpses of how the subunits interact to enable the translation of messenger RNA into protein.

Also notable is the number of membrane protein structures solved in the past year. In February, Nigel Unwin reported a refined (but still rather low-resolution) structure of the channel domain of the nicotinic acetylcholine receptor (2BG9). Together with the much older structure of snail acetylcholine binding protein, this completes the first full experimental structural model of an ion channel gated by a small molecule, as Roderick MacKinnon's highly controversial structure of the KvAP potassium channel did for voltage gating in 2003. In addition, several new structures of acetylcholine binding proteins with different ligands have been recently published (2BYN, 2BYP, 2BYQ, 2BYR, 2BYS).

While the structural biology of coupled transporters was kicked off when the atomic-resolution structures of two members of the major facilitator superfamily were reported in the August 1, 2003 issue of Science, 2005 has been an especially important year in this area. The structure of a Na+/H+ antiporter was released in July (1ZCD), followed closely by the publication by Eric Gouaux and co-workers at Columbia University of the structure of a bacterial glutamate transporter related to those found in the nervous system, albeit at modest resolution (1XFH). Not to be outdone, however, the same group followed this closely by the structure of a very different transporter. In a paper likely to excite pharmaceutical companies, and some neurobiologists and psychoactive drug enthusiasts, worldwide, they revealed a 1.65 Angstrom resolution structure of a prokaryotic leucine transporter having 20-25% homology to the neuronal reuptake transporters for the neurotransmitters serotonin, dopamine, norepinephrine, and gamma-aminobutyric acid (GABA) (2A65). All of these transporters have different and previously unknown folds.

Though not of exceptional structural interest per se, the structures of SARS coronavirus protease in complex with designed inhibitors (2AMD, 2AMQ, 2D2D) are significant in that they exemplify the increasingly common and rapid application of structural biology in medicine.