Thursday, October 8, 2009

Chemistry Nobel Prize 2009

Venkatraman Ramakrishnan, Thomas Steitz, and Ada Yonath

Just as architects usually get more glory than carpenters, DNA is more famous than the molecular machine that converts genetic blueprints into proteins. But the ribosome is in the limelight today with the announcement of this year's Nobel Prize in chemistry.

The prize was awarded to three scientists who revealed the atomic structure and inner workings of the ribosome: Ada Yonath of the Weizmann Institute of Science in Rehovot, Israel; Thomas Steitz of Yale University; and Venkatraman Ramakrishnan of the Medical Research Council Laboratory of Molecular Biology in Cambridge, United Kingdom. All three used a technique known as x-ray crystallography to pinpoint the position of thousands of atoms in the cellular machine known as the ribosome, and all will share one-third of the $1.4 million prize.

"It's a fantastic accomplishment and one that everyone in the field has known for some time is worthy of such recognition," says Wayne Hendrickson, an x-ray crystallographer at Columbia University. Hendrickson adds that this year's prize also completes the Nobel Committee's recognition for the discoverers of biology's central dogma, which describes how genetic information in DNA is copied into RNA, which is then translated into proteins. In 1962, James Watson, Francis Crick, and Maurice Wilkins were awarded the Nobel for their atomic model of DNA. In 2006, Roger Kornberg won for his x-ray structures of DNA polymerase, which translates DNA into RNA. Today's prize for work on the ribosome, completes that, Hendrickson says.

Ribosomes exist in all cells in all living organisms. Although central, they are anything but simple. Dozens of different proteins and strands of RNA form a complicated machine divided into two principle components. The smaller component, known as the 30S subunit, works mainly to decode the genetic code in messenger RNA. The larger 50S subunit then takes this information and uses it to stitch together the proper sequence of amino acids that make up the final protein. Early on, researchers struggled to map the atomic structure of even one of these subunits. Producing an x-ray structure requires first creating crystals of millions of copies of a ribosome aligned in near perfect order. If that ordering is precise enough, researchers can then fire a beam of x-rays at the crystal. The pattern in which those x-rays then deflect off the crystal can then be used to map out the arrangement of atoms in the molecule.

In 1980, Yonath managed to generate the first low-quality crystals of a ribosome. By 1990, she had upped the quality of her crystals, but she still struggled to a good structure. Steitz, along with his longtime Yale colleague Peter Moore, jumped into the fray in 1995, following Yonath's recipe for making ribosomal crystals. By 1998, they used additional insights gleaned from electron microscopy studies to help them acquire a low-resolution 9 Angstrom structure of the ribosome. In August, 2000 Steitz's group then published a higher 2.4 Angstrom resolution structure of the large subunit (Science, 11 August 2000, p. 905). Meanwhile, Yonath's and Ramakrishnan's groups published slightly lower resolution structures of the smaller subunit the following month. Since then, the three groups, plus other teams, have used those structures and others to understand in atomic detail how ribosomes translate genetic information into proteins.

The three groups have also begun to push practical applications of their work. All three, for example, have reported crystal structures that show how different antibiotics bind to the ribosome. And several companies are now using these structures in an effort to design new antibiotics against worrisome infections, such as methicillin-resistant Staphylococcus aureus and tuberculosis.

But Steitz, for one, says he never thought initially that anything more than a fundamental insight into the molecular workings of biology would come of the work. "It seemed a bit like trying to climb Mount Everest," Steitz says. "We knew it was doable. But we didn't know how to get there. When we got there in 2000, it was exhilarating. In fact, it was the most exhilarating moment I've had in science."

1 comment:

Dale Ritter said...

Mapping the atomic level of ribosomal structure is noteworthy, contemporary thought. This all devolves to the data density factor in research, which recently gained development to the stage of the picoyoctometric, 3D, interactive video atomic model imaging equation named the GT integral.
The atom's RQT (relative quantum topological) data point imaging function is built by combination of the relativistic Einstein-Lorenz transform functions for time, mass, and energy with the workon quantized electromagnetic wave equations for frequency and wavelength. The atom labeled psi (Z) pulsates at the frequency {Nhu=e/h} by cycles of {e=m(c^2)} transformation of nuclear surface mass to forcons with joule values, followed by nuclear force absorption. This radiation process is limited only by spacetime boundaries of {Gravity-Time}, where gravity is the force binding space to psi, forming the GT integral atomic wavefunction. The expression is defined as the series expansion differential of nuclear output rates with quantum symmetry numbers assigned along the progression to give topology to the solutions.
Next, the correlation function for the manifold of internal heat capacity particle 3D functions is extracted by rearranging the total internal momentum function to the photon gain rule and integrating it for GT limits. This produces a series of 26 topological waveparticle functions of the five classes; {+Positron, Workon, Thermon, -Electromagneton, Magnemedon}, each the 3D data image of a type of energy intermedon of the 5/2 kT J internal energy cloud, accounting for all of them.
Those energy data values intersect the sizes of the fundamental physical constants: h, h-bar, delta, nuclear magneton, beta magneton, k (series). They quantize nuclear dynamics by acting as fulcrum particles. The result is the picoyoctometric, 3D, interactive video atomic model data point imaging function, responsive to keyboard input of virtual photon gain events by relativistic, quantized shifts of electron, force, and energy field states and positions.
Images of the h-bar magnetic energy waveparticle of ~175 picoyoctometers are available online at with the complete RQT atomic modeling guide titled The Crystalon Door, copyright TXu1-266-788. TCD conforms to the unopposed motion of disclosure in U.S. District (NM) Court of 04/02/2001 titled The Solution to the Equation of Schrodinger.