Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

NMR Method Rapidly Solves 8 Target Genomic Structures

19.07.2005


High throughput method is very versatile, signals a new era for NMR



University at Buffalo scientist created a stir in 2003 when he announced a much faster, more precise and far less expensive method of obtaining nuclear magnetic resonance (NMR) data to map a protein’s atomic structure. Genomics researchers were fascinated, but some also were a bit skeptical.

Not anymore.


In the current issue of Proceedings of the National Academy of Sciences, Thomas A. Szyperski, Ph.D., UB professor of chemistry, and a team of structural genomics scientists present a paper on how they determined the structures of eight proteins in just 10-20 days per protein.

Researchers typically need an average of six to 12 months to solve a single protein using conventional NMR methods.

The publication proves the efficacy of Szyperski’s patented protocol to solve protein structures, with the ultimate goal of developing new medicines and treatments.

It also marks the beginning of wider dissemination and use of his method, called GFT-NMR, (G-matrix Fourier Transform NMR) to solve protein structures, including membrane proteins, considered by some to be the "holy grail" of structural genomics and highly prized in rational drug design.

"This is the type of innovative methodology development that’s crucial for achieving the goals of the Protein Structure Initiative and advancing structural biology," said John Norvell, Ph.D., director of the Protein Structure Initiative (PSI) of the National Institute of General Medical Sciences of the NIH.

The authors of the PNAS paper are supported by the National Institutes of Health-funded Northeast Structural Genomics Consortium (NESG), part of the PSI.

"This publication in PNAS completes the story by showing that the method works almost better than we expected and is applicable broadly to solve structures of proteins with 200 amino acid residues or more," said Szyperski, who was named one of Scientific American magazine’s top 50 technology leaders in 2003.

Already, Szyperski’s method has been used to solve more than a dozen structures. He expects his lab at UB to solve between 12 and 15 structures per year, using GFT-NMR.

NMR machines use very powerful magnetic fields to determine macromolecular structures. Experiments involve first measuring the chemical shifts or resonance frequencies of a structure’s atomic nuclei. These measurements are obtained by NMR spectra experiments in which resonance frequencies are measured and correlated, and which are then used to measure distances between protons in order to calculate the molecular structure.

GFT-NMR can be used for both steps, as described in three papers the UB group published within the past year in PNAS and the Journal of the American Chemical Society.

"It’s clear now that NMR is a very nice complement to crystallography," said Szyperski, who has joint appointments in the departments of biochemistry and structural biology in the UB School of Medicine and Biomedical Sciences, as well as in the College of Arts and Sciences. "There are many high-profile proteins that don’t crystallize or don’t do so easily. For X-ray crystallography-based, high-throughput structural biology, this is a major obstacle."

For example, in a paper currently in press in Proteins, Szyperski’s lab used GFT-NMR to solve a protein target in just two weeks that the Midwest Center for Structural Genomics, a major center of the PSI, had been unable to solve using X-ray crystallography.

Szyperski, who is director of the NESG’s NMR division, noted that NESG is the only large-scale center funded by the Protein Structure Initiative with a strong NMR component.

"NESG is starting to operate as an NMR branch for the other structural genomics consortia that are focused exclusively on crystallography," said Gaetano T. Montelione, Ph.D., professor of molecular biology and biochemistry at Rutgers, the State University of New Jersey, director of NESG and a co-author.

"The protocol described in the PNAS paper is of high value for NMR-based structural genomics pursued by the NMR division of the Northeast Structural Genomics Consortium and nicely exemplifies the combined use of GFT-NMR, highly sensitive modern NMR spectrometers equipped with ’cryogenic probes’ and methodology for semi-automated data analysis," said Montelione.

His laboratory at Rutgers was the major supplier of proteins for the research published in PNAS. The Rutgers group also has developed some of the essential tools for semi-automated analysis of NMR data used in the work.

"Our labs collaborate very intensely on developing methodologies for semi-automated data analysis," said Szyperski, "an important cross fertilization for efficient structure calculation.

"Using our automated analysis methods, initial 3D protein structures could be generated soon after data collection and then refined by manual data-analysis methods," said Montelione.

Proteins also were supplied by a team led by Cheryl Arrowsmith, Ph.D., professor in the Department of Medical Biophysics at the University of Toronto, and including Adelinda Yee, Ph.D., scientific associate, and Alexander Lemak, Ph.D., research associate, co-authors at U of T.

Computing power for the calculation of so many structures in such a short time was provided by the Center for Computational Research, part of UB’s New York State Center of Excellence in Bioinformatics and Life Sciences.

Szyperski’s success has attracted approximately $4 million in new federal research funds to his lab at UB over the next five years from the Protein Structure Initiative of which the NESG is a part; from the New York Center on Membrane Protein Structure, an NIH-funded center of the PSI, and the Molecular and Cellular Biophysics Division of the National Science Foundation.

Critical support for the early development of Szyperski’s method came from the National Science Foundation’s Molecular and Cellular Biophysics Division, led by Kamal Shukla, Ph.D., program director.

UB has provided support for the maintenance of the NMR facility, as well as generous matching funds to purchase a new ultra-sensitive cryogenic NMR probe, which boosts the instrument’s sensitivity.

Additional UB co-authors on the PNAS paper and members of the Szyperski lab are Hanudatta S. Atreya, Ph.D., and Gaohua Liu, Ph.D., senior research scientists; Yang Shen, Ying Shao and David Parish, graduate students, and Dinesh K. Sukumaran, Ph.D., director of the Magnetic Resonance Center in the Department of Chemistry.

Co-authors at the Center for Advanced Biotechnology and Medicine, a joint operation of Rutgers and the University of Medicine and Dentistry of New Jersey, are Rong Xiao, laboratory researcher; Aneerban Bhattacharya, doctoral candidate, and Thomas Acton, Ph.D., assistant research professor.

The University at Buffalo is a premier research-intensive public university, the largest and most comprehensive campus in the State University of New York.

Ellen Goldbaum | EurekAlert!
Further information:
http://www.buffalo.edu

More articles from Life Sciences:

nachricht A Map of the Cell’s Power Station
18.08.2017 | Albert-Ludwigs-Universität Freiburg im Breisgau

nachricht On the way to developing a new active ingredient against chronic infections
18.08.2017 | Deutsches Zentrum für Infektionsforschung

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Fizzy soda water could be key to clean manufacture of flat wonder material: Graphene

Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.

As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...

Im Focus: Exotic quantum states made from light: Physicists create optical “wells” for a super-photon

Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.

Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...

Im Focus: Circular RNA linked to brain function

For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.

While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...

Im Focus: RAVAN CubeSat measures Earth's outgoing energy

An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.

The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...

Im Focus: Scientists shine new light on the “other high temperature superconductor”

A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.

Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Call for Papers – ICNFT 2018, 5th International Conference on New Forming Technology

16.08.2017 | Event News

Sustainability is the business model of tomorrow

04.08.2017 | Event News

Clash of Realities 2017: Registration now open. International Conference at TH Köln

26.07.2017 | Event News

 
Latest News

A Map of the Cell’s Power Station

18.08.2017 | Life Sciences

Engineering team images tiny quasicrystals as they form

18.08.2017 | Physics and Astronomy

Researchers printed graphene-like materials with inkjet

18.08.2017 | Materials Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>