Nuclear magnetic resonance studies on the 1,2;5,6-di-0-isopropylidene-D-hexofuranose sugars have provided information on the conformational preferences of the five-membered rings in these molecules. They appear to have strong conformational preferences rather than existing as freely pseudorotating systems. The furanose rings of the 3-deoxy-ribo and lyxo derivatives are found to preferentially exist in an envelope conformation in which C 4 is displaced from the plane of the ring. The arabino and xylo derivatives are found to be much less distorted, with preferred conformations approaching twist forms involving displacements of C-1 and -2. Substitution of various endo and exo groups at C-3 appears to have only minor influence on the parent furanose conformation.Les etudes r.m.n. sur les sucres de la serie des di-0-isopropylidine-1 ,2;5,6-D-hexofuranoses ont fourni des renseignements sur les conformations privilegites des cycles a cinq dans ces mol6cules. PlutBt que d'etre en pseudo-rotation libre, ces systemes apparaissent sous des conformations nettement prkfkrentielles. Les cycles furanoses des derives dtoxy-3 rib0 et Iyxo existent preferentiellement dans la conformation enveloppe dans laquelle le C 4 est au dehors du plan du cycle. Les derives arabino et xylo sont nettement moins tordus et adoptent la conformation privilkgik proche des formes "twist" impliquant les dkplacements des C-1 et -2. La substitution des divers groupes endo et exo sur le C-3 semble n'avoir qu'une influence mineure sur la conformation du furanose parent.

The growth factor receptor-bound protein-2 (Grb-2) is an adaptor protein that mediates signal transduction pathways. Chemical shift assignments were obtained for the SH2 domain of Grb2 by heteronuclear NMR spectroscopy, employing the uniformly 13C-/15N-enriched protein as well as the protein containing selectively 15N-enriched amino acids. Using the Chemical Shift Index (CSI) method, the chemical shift indices of four nuclei, 1H alpha, 13C alpha, 13C beta and 13CO, were used to derive the secondary structure of the protein. Nuclear Overhauser enhancements (NOEs) were then employed to confirm the secondary structure. The CSI results were compared to the secondary structural elements predicted for the Grb2 SH2 domain from a sequence alignment [Lee et al. (1994) Structure, 2, 423-438]. The core structure of the SH2 domain contains an antiparallel beta-sheet and two alpha-helices. In general, the secondary structural elements determined from the CSI method agree well with those predicted from the sequence alignment.

A set of high-resolution three-dimensional solution structures of the Src homology region-2 (SH2) domain of the growth factor receptor-bound protein-2 was determined using heteronuclear NMR spectroscopy. The NMR data used in this study were collected on a stable monomeric protein solution that was free of protein aggregates and proteolysis. The solution structure was determined based upon a total of 1439 constraints, which included 1326 nuclear Overhauser effect distance constraints, 70 hydrogen bond constraints, and 43 dihedral angle constraints. Distance geometry-simulated annealing calculations followed by energy minimization yielded a family of 18 structures that converged to a root-mean-square deviation of 1.09 A for all backbone atoms and 0.40 A for the backbone atoms of the central beta-sheet. The core structure of the SH2 domain contains an antiparallel beta-sheet flanked by two parallel alpha-helices displaying an overall architecture that is similar to other known SH2 domain structures. This family of NMR structures is compared to the X-ray structure and to another family of NMR solution structures determined under different solution conditions.

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