This Article Figures Only Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a colleague Companion article to this Commentary Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Add to My File Cabinet Download to citation manager Request Copyright Permission Citing Articles Citing Articles via CrossRef Google Scholar Articles by Gryk, M. R. Articles by Hoch, J. C. PubMed PubMed Citation Articles by Gryk, M. R. Articles by Hoch, J. C. Social Bookmarking                What's this?

 Previous Article  | Table of Contents |  Next Article 

COMMENTARY
Local knowledge helps determine protein structures

Michael R. Gryk and Jeffrey C. Hoch^*

Department of Molecular, Microbial, and Structural Biology, University of Connecticut Health Center, Farmington, CT 06030-3305

The nuclear Overhauser effect (NOE) has been the workhorse of structural studies of macromolecules in solution by NMR spectroscopy. The NOE is a measure of the rate of magnetization transfer between nuclei, induced by modulation of the magnetic dipole–dipole coupling between nuclear spins by overall tumbling of the molecule in solution (1). The efficiency of magnetization transfer via this mechanism is low; consequently, NOEs are typically only observed for protons within 5 Å, and lengthy experiments are required in order to detect the weak effect. NOE magnitudes provide a "spectroscopic ruler" through the approximate r^–6 dependence on the distance between proton pairs. Although it takes surprisingly few such distance estimates to determine the overall fold of a protein (2)—provided the estimates are distributed evenly throughout the protein—even a complete set of NOEs yields far fewer constraints on the structure than are required to determine all 3N – 6 degrees of freedom for an N-atom protein. The fold is even more highly underdetermined when protein flexibility is taken into account. By complementing NMR measurements with prior knowledge of protein structure, usually in the form of a potential energy function that describes the physical plausibility of a model structure, NMR has emerged as a valuable complement to x-ray crystallography for structure determination. The Protein Data Bank (PDB) (3) now contains >7,000 NMR protein structures, and >1,000 new structures are anticipated to be added in 2008. One way to further hasten the rate of protein structure determination by NMR is to develop alternatives that avoid the need to measure and assign NOEs. In this issue of PNAS, Shen et al. (4) describe a viable alternative to NOE-based structure determination for small proteins.

Nevertheless, reliance on NOEs for determination of biomolecular structure presents real . . . [Full Text of this Article]

*To whom correspondence should be addressed. E-mail: hoch@uchc.edu

CiteULike    Complore    Connotea    Del.icio.us    Digg    What's this?

Companion article to this Commentary:

From the Cover: Consistent blind protein structure generation from NMR chemical shift data

Yang Shen, Oliver Lange, Frank Delaglio, Paolo Rossi, James M. Aramini, Gaohua Liu, Alexander Eletsky, Yibing Wu, Kiran K. Singarapu, Alexander Lemak, Alexandr Ignatchenko, Cheryl H. Arrowsmith, Thomas Szyperski, Gaetano T. Montelione, David Baker, and Ad Bax
PNAS 2008 105: 4685-4690. [Abstract] [Full Text]