Ribosome stalling as gene regulation?

Another cool paper from Mankin lab showed up in Nature Chemical Biology. This time researchers were looking at the detailed mechanism of translational arrest by two macrolide antibiotics, erythromycin and telithromycin.

ERY-TEL

Via series of mutations authors identified a single amino acid in the nascent peptide chain that determines selectivity and promiscuity of ribosome stalling by either of two antibiotics. To prove their point, they created an unnatural mutant gene with engineered selectivity to TEL.

While major implications of the study are dealing with antibiotic resistance and ways to overcome it, the authors coin an interesting evolutionary speculation. They suggest that the ribosome stalling could be another mechanism for gene regulation. In this case the sequence of some peptides could evolve in order to recognize small molecules during translation of the protein itself. And this could be another way to react on the environmental stimuli.

I guess that calls for another whole-transcriptome and cross-species genomic mining study for identification of such sequence−cofactor pairs.

By the way, a rare case, they did molecular dynamics simulation but didn’t include any pretty picture from it in the main text of the manuscript! That’s what happening when one has enough experimental data.

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OC tidbits #4

Büschleb et al. (ACIE)

A collection of OC tidbits selected by Hanessian and Overman groups. Featuring a dozen of natural products, each full of densely-packed stereocenters; 29 oldschoolishly lengthy synthetic schemes including three hundred intermediates that undergo all sorts of electrocyclic reactions and crazy cascades. Read in limited quantities to prevent overexcitement.

And, of course, I liked this guy (or girl?) at the frontispiece (the only thing one can get for free from Angewandte preview without subscription) in high-energy conformation overcoming some activation barrier.

completedSyn

Nicolaou et al (JACS)

KCN loves gold.

nicolaou-2

Picado et al. (JOC)

Turning failures into victories: if the reaction works, it’s just another row in a table. If it doesn’t, it can be a whole new paper!

joc-fail

Pan, Qin et al. (Org Lett)

A question without answer: how come this stereochemistry

panqin.png

… given this:

panqin2.png

 

Patil et al. (JOC)

Simplicity is the new beauty (via orgchem.by).

oximes

Mishra and Biswas (JOC)

Another example of beautiful simplicity.

mishra.png

Babij, McCuscer et al. (OPR&D)

Expanded list of chemical shifts for commond (and not so common but green) solvents [open access!]

op-2015-00417r_0006

 

 

Thesis in LaTeX.

The background.

When I was writing my diploma thesis in 2009, I wanted to do it somewhat ‘special’ and I tried to write it in LaTeX (more precisely in LyX). That time there were so many geeks around Internet that praised LaTeX to be superior to any other typesetting method that I was eventually persuaded to give it a try. That time I failed miserably. Eventually I ended up writing the diploma in OpenOffice (currently LibreOffice).

Four years later I again faced the choice: either to take an easy way and to compile the PhD thesis in MS Word, or to overcome the challenge of steep learning curve of LaTeX.

Continue reading “Thesis in LaTeX.”

Epi-epigenetics: RNA methylation (updated)

Two papers appeared online on February 10th, to claim the first whole-transcriptome study of specific RNA modification, N1-methylation of adenine (m1A). To both teams’ credits, they cited each other as they learned about “competing” study.  Both papers, Li, Xiong et al. in Nature Chemical Biology and Dominissini, Nachtergaele, Moshitch-Moshkovitz et al. in Nature, overlap quite significantly but also complete each other in several aspects, and give starting insights into the role of RNA methylation in gene regulation. Continue reading “Epi-epigenetics: RNA methylation (updated)”

Catching gravitational waves

OK, seems like I am on a track of rebuilding my daily routine under new circumstances of the offline life. So it’s a good time to incorporate some blogging activity in it.

While I was away, some fascinating things happened. First of all I mean the direct observation of gravitational waves, which were theoretically predicted by Einstein in 1915 (or Poincare in 1905, if you stretch your definition of “prediction”). As with all fundamental physics experiments, the measurement was not a trivial one. It required construction of two interferometers each having two orthogonal 4 km-long tubes to detect distortion of the spacetime by a fraction of a proton diameter. Continue reading “Catching gravitational waves”

True power of 1D NMR

An interesting case study of a correct structure assignment for aquatolide appeared in JOC. It’s interesting from several points of view. First, it nicely shows how one can effectively use reach information from free induction decay (FID), which is lost (or masked) in Fourier-transformed spectra. Second, it emphasizes importance of data sharing and demonstrates crucial role of ‘research parasites‘ in scientific ecosystem. Third, the paper has seven-point manifest in the conclusions section. Continue reading “True power of 1D NMR”

OC tidbits #3

Giantassio, Lopchuk et al. (Baran lab) (Science)

As the legend goes, people from Pfizer approached Phil Baran and told him “You know, we figured out what our problem is. We need more propellers on our molecules.” Phil said “OK,  sounds like a good project” and put two grad students on it. Results: the 3-in-1 Science paper, with propellers spinning on every amine, SI, which is longer than my PhD thesis, and happy Pfizer counting cash.

slide1
Propellers everywhere! Source

By the way, Baran lab has a cold room for synthesis.

cold_room

 Qi et al. (Porco lab) (JACS)

Electrocyclic reactions are always fun, especially when 2 in 1. See the paper for stereoselective one.

electrocyclic

Schuler et al. (Nat Chem)

How to monitor progress of Bergman cyclization at 1.66 yoctomole scale? Atomic force microscopy is the answer.

reverse-bergman-cyclisation_nchem_2438_auproof-toc_630m

Zhao, Ming et al. (Org Lett)

Looks trivial until you try to push the electrons. The side-product hints at the mechanism.

zhao

Feng et al. (Tet Lett)

Another magic reaction candidate for debunking? Thanks sash-2003 for heads up.

1-s2-0-s0040403916300089-fx1

And before you rush to check it, they do report detection of molecular hydrogen in the gas mixture coming from the reaction.

hydrogen

 

 

Short life of biological dogmas

When you read a molecular biology textbook, it’s hard not to be amazed by the elegance and precision of cellular machinery. Everything is so logical, sequential, and organized to work properly. DNA templates self-copy and encodes RNA, which encodes proteins that do all kinds of work in a cell and organism. Francis Crick, who postulated this sequence, coined a term ‘the central dogma’ for it. And ever since ‘dogma’ became a buzzword for any fundamental assumption in molecular biology. But as with many assumptions in physics in the beginning of XX century, now many of these biological ‘dogmas’ are becoming obsolete. A recent review in Nuclear Acids Research discusses the premises for another dogma to fall.
Continue reading “Short life of biological dogmas”

Research parasites

It’s really entertaining to watch the (over)reaction of Twitter on the controversial editorial in NEJM about data sharing and open science. As usual, it’s pretty hysteric but has a potential to cause some real-world consequences. The problem is that the authors were reckless enough to use term “research parasites” for those scientists who use the data from other labs without conducting their own experiments. Continue reading “Research parasites”

High-level scientific miscommunication

There’s a scandal growing in the field of CRISPR due to a lawsuit and patent war between pioneers of the technology. And then this paper in Cell appeared and made the things worse… I don’t want do discuss in details the story behind, because there are plenty of better information sources all over the internet. What I want to bring up today is the problem of communication in the highest level of science, among respected professors.

Continue reading “High-level scientific miscommunication”