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Top 7 in Biochemistry

A snapshot of the most highly ranked articles in biochemistry and related areas, from Faculty of 1000

By | October 24, 2011

WELLCOME LIBRARY, LONDON

1. Lighting up RNA
A novel technique for tagging and following RNA processes in live cells promises to illuminate RNA biology the way green fluorescent protein (GFP) did for the study of proteins. The tagging method consists of short RNA sequences that bind to GFP-like fluorophores and produce a wide range of colors. These RNA-fluorophore complexes can then be fused to RNAs in the cell.

J.S. Paige et al., “RNA mimics of green fluorescent protein,” Science, 333:642-46, 2011. Free F1000 Evaluation

2. G-coupled proteins unveiled
Researchers used a series of techniques to reveal the structure of a G-protein coupled receptor, called the beta-2 adrenergic receptor-Gs protein complex, which belongs to a class of receptors that drives cellular responses to hormones and plays a role in sight, smell, and taste. The receptor's crystal structure  reveals a specific surface of the protein complex that may modulate receptor signaling.

S. Rasmussen, et. al, “The crystal structure of the beta-2 adrenergic receptor-Gs protein complex,” Nature, 0.1038/nature10361, 2011. Free F1000 evaluation.

3 & 4. Cancer drug effectiveness probed
Researchers at F1000 are still talking about two papers published in 2004, which solved the mystery of why the anticancer drug gefitinib (brand name Iressa)—which works by latching on to the ATP-binding site of the epidermal growth factor receptor (EGFR)—is effective in only 10 percent of patients with non-small cell lung carcinoma even though EGFR is overexpressed in over 70 percent of patients with that cancer type. It turns out that gefitinib is only effective in those patients with rare mutations that affect the amino acids in the ATP-binding region of EGFR. The findings have since resulted in a more patient-specific use of the drug.

J.G. Paez et al., “EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy,” Science, 304:1497-500, 2004. Free F1000 evaluation

T.J. Lynch et al., “Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib,” N Engl J Med, 350: 2129-39, 2004. Free F1000 evaluation

5. Screening for antimalarial drugs
By screening approximately 1.7 million small molecules for the ability to inhibit the growth of Plasmodium falciparum in red blood cells, researchers not only identified around 6,000 compounds with the potential of antimalarial activity, but they were able to computationally predict the putative mechanisms of actions for some.

D. Plouffe et al., “In silico activity profiling reveals the mechanism of action of antimalarials discovered in a high-throughput screen,” Proc Natl Acad Sci, 105:9059-9064, 2008. Free F1000 evaluation

6. Cryogenic cooling of proteins on hot water
A comparison of X-ray diffraction data of 30 proteins that had either been crystallized at cryogenic temperatures or kept in ambient-temperature solutions revealed that the common process of cryocooling offers a poorer view of protein structural dynamics. The process fails to reveal, for example, variable conformations of amino-acid side chains, suggesting that X-ray diffraction data obtained at room temperature may better suited for revealing the motions and substates of proteins important for catalysis and function.

J.S. Fraser, “Accessing protein conformational ensembles using room-temperature X-ray crystallography,” Proc Natl Acad Sci, 108:16247-52, 2011. Free F1000 evaluation

7. Promising antimalarial compound found
A high-throughput screening of 12,000 molecules with activity against Plasmodium falciparum and Plasmodium vivax led researchers to identify a new class of compounds known as spiroindolones which are effective antimalarials at nanomolar concentrations. The star of the pack was the synthetic compound NITD609, which affected all stages of the parasites’ life cycles by blocking protein synthesis.

M. Rottmann et al., “Spiroindolones, a potent compound class for the treatment of malaria,” Science, 329:1175-80, 2010. Free F1000 evaluation

The F1000 Top 7 is a snapshot of the highest ranked articles from a 14-day period on Faculty of 1000 Biochemistry, as calculated on October 21, 2011. Faculty Members evaluate and rate the most important papers in their field. To see the latest rankings, search the database, and read daily evaluations, visit http://f1000.com.

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Comments

Avatar of: Len Banaszak

Len Banaszak

Posts: 6

October 27, 2011

Forgive me for i haven't read the entire paper on cryogenics and crystallography.  No doubt the low temperature methods do introduce new variables.  However without low temperature data, one must find an alternate way of dealing with radiation damage and the absence of very high resolution data.  The effect of cryoprotectants in general appears to be of minor significance (for most crystalline specimens).  Damned if you do and damned if you don't. I still would choose the cryogenic model for further study!

Avatar of:

Posts: 0

October 27, 2011

Forgive me for i haven't read the entire paper on cryogenics and crystallography.  No doubt the low temperature methods do introduce new variables.  However without low temperature data, one must find an alternate way of dealing with radiation damage and the absence of very high resolution data.  The effect of cryoprotectants in general appears to be of minor significance (for most crystalline specimens).  Damned if you do and damned if you don't. I still would choose the cryogenic model for further study!

Avatar of:

Posts: 0

October 27, 2011

Forgive me for i haven't read the entire paper on cryogenics and crystallography.  No doubt the low temperature methods do introduce new variables.  However without low temperature data, one must find an alternate way of dealing with radiation damage and the absence of very high resolution data.  The effect of cryoprotectants in general appears to be of minor significance (for most crystalline specimens).  Damned if you do and damned if you don't. I still would choose the cryogenic model for further study!

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