Nuclear magnetic resonance spectroscopy protein structure determination

Amazaki TY, Hinck AP, Wang XY, Nicholson LK, Torchia DA, Wingfield P, Stahl SJ, Kaufman JD, Chang CH, Domaille PJ, Lam PY, Three-dimensional solution structure of the HIV-1 protease complexed with DMP323, a novel cyclic urea-type inhibitor, determined by nuclear magnetic resonance spectroscopy, Protein Sci., 5 495-506, 1996. 

GM Clore, MA Robien, AM Gronenborn. Exploring the limits of precision and accuracy of protein structures determined by nuclear magnetic resonance spectroscopy. J Mol Biol 231 82-102, 1993. 

Wiithrich, K. Protein structure determination in solution by nuclear magnetic resonance spectroscopy. Science 243 45-50, 1989. 

Another method of determining the secondary and tertiary structure of a protein is NMR (nuclear magnetic resonance) spectroscopy. NMR spectroscopy reveals detailed information on specific sites of molecules without having to solve then-entire structure. 

Wuthrich, K. Protein Structure Determination in Solution by Nuclear Magnetic Resonance Spectroscopy, Science, 45 (1989). 

Most of our structural information comes from x-ray crystallographic analysis of protein crystals and from the use of nuclear magnetic resonance spectroscopy in solution. Each of these techniques has advantages and limitations which makes them suitable for a complementary range of problems. The first protein structure determined at a sufficient resolution to trace the path of the polypeptide chain was that of myoglobin in 1960. Since that time many thousands of structures corresponding to hundreds of different proteins have been determined. The coordinates of the atoms in many protein and nucleic acid structures are available from the Protein Data Bank, which may be accessed via the Internet or World Wide Web (http //www.pdb.bnl.gov). 

G. M. Clore and A. M. Gronenborn, CRC Crit. Rev. Biochem., 24,479 (1989). Determination of the Three Dimensional Structures of Proteins and Nucleic Acids in Solution by Nuclear Magnetic Resonance Spectroscopy. 

H. Widmer, M. Billeter, and K. Wiithrich, Proteins, 6, 357 (1989). Three-Dimensional Structure of the Neurotoxin ATX la from Anemonia sulcata in Aqueous Solution Determined by Nuclear Magnetic Resonance Spectroscopy. 

A crucial question is. What does the three-dimensional structure of a specific protein look like Protein structure determines function, given that the specificity of active sites and binding sites depends on the precise threedimensional conformation. Nuclear magnetic resonance spectroscopy and x-ray crystallography are two of the most important techniques for elucidating the conformation of proteins. 

R542 N. J. Skelton and W. J. Chazin, Solution Structure Determination of Proteins by Nuclear Magnetic Resonance Spectroscopy , Drugs Pharm. Sci., 2000,101, 683... 

Over the past 50 years, spectacular advances have been made in X-ray diffraction, nuclear magnetic resonance spectroscopy, and several other techniques for determining structure. Theoretical studies of polymers have also been developing at a rapid pace with faster and more advanced computing capability. There is much interest at the moment in the possibility of using biological molecules such as proteins and DNA as electrical conductors. The possibility... 

Other techniques for the bioanalytical characterisation of allergenic proteins and for the elucidation of the tertiary stmcture are nuclear magnetic resonance spectroscopy and x-ray structure analysis, in which separated or purified proteins are used. The two techniques are still the only methods available for a determination of the stmcture of macromolecules such as proteins and nucleic acid on an atomic level, but are usually not utilized in standard food analysis. Both methods have been employed successfully in the elucidation of allergenic proteins [33,34]. 

Pfander R, Neumann L, Zweckstetter M, Seger C, Holak TA, Tampe R (1999) Structure of the active domain of the herpes simplex virus protein ICP47 in water/sodium dodecyl sulfate solution determined by nuclear magnetic resonance spectroscopy. Biochemistry 38 13692 13698 Ploegh HL (1998) Viral strategies of immune evasion. Science 280 248- 253... 

K. Wiithrich, Acc. Chem. Res., 22, 36 (1989). The Development of Nuclear Magnetic Resonance Spectroscopy as a Technique for Protein Structure Determination. 

Nuclear magnetic resonance spectroscopy, or NMR, is the most valuable of the numerous spectroscopic techniques used for structure determination. Although we focused in this chapter on NMR applications to small molecules, more advanced NMR techniques are also used in biological chemistry to study protein structure and folding. 

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