Comparison of protein structures determined by NMR in solution and by X-ray diffraction in single crystals

Abstract

Following the first determinations of protein structures in the late 1950s and the early 1960s (see for example Kendrewet al.1960; Perutz, 1964), the three-dimensional structures of several hundred proteins have been elucidated by X-ray diffraction on single crystals. By the end of 1991, approximately 150 entries of proteins with substantially different sequences and a well resolved structure (Hobohmet al.1992) were deposited in the Protein Data Bank (Bernsteinet al.1977; Abolaet al.1987). In addition, many structures of homologous proteins or of mutants have been described, bringing the total number of entries to about 600. While it was soon accepted that almost all of these structures do indeed give a correct picture of the fold of the active protein in spite of the non-physiological environment of single crystals, it is not clear to what extent structural details are reliably described by these structures. In particular the surface of a protein may be modified due to the dense packing of protein molecules in the crystal lattice. A detailed knowledge of the protein surface is, however, essential for the understanding of the function of the protein.

NMR – this other method for protein and nucleic acid structure determination

“…19) particularly detailed comparisons of the two states have been made, which also includes solving the crystal structure by molecular replacement with the NMR structure (Braun, Epp, Wiithrich & Huber, 1989). Some general observations emerged from the analyses of these two proteins that have been found to be true generally for globular proteins (Billeter, 1992). The dominant impression is one of near-identity of the molecular architecture in solution and in single crystals (Fig.…”

“…By now a significant number of globular proteins are available for which structures have independently been determined in crystals and in solution (for a recent review, see Billeter, 1992). For Tendamistat (Fig.…”

“…In some cases these differences could be attributed unambiguously to protein-protein contacts in the protein crystals (e.g. Billeter, 1992).…”

“…Starting in 1990, the publication of an annual survey of new experimental macromolecular [1990][1991][1992][1993] Structures determined by X-ray crystallography, NMR or by any other method are listed separately. The data are from Hendrickson & Wtithrich (1991, 1992, 1994 (Hendrickson & Wiithrich, 1991, 1992, 1994 provides a guide to the contributions by the different techniques available ( Table 1). The few entries in the 'Other methods' column of Table 1 refer to structures solved by X-ray fibre diffraction or electron diffraction in crystals.…”

Localized solution structure refinement of an F45W variant of ubiquitin using stochastic boundary molecular dynamics and NMR distance restraints

“…More generally, in a survey of 12 proteins whose structures were independently determined by both NMR and single crystal diffraction, Billeter (1992) found a high degree of similarity between structures produced by each method. Where they were noted, discrepancies were attributed to genuine disorder (as for side chains on the surface), improper use of H-bond restraints in the NMR refinement, perturbations from small co-crystallizing ions, and from crystal lattice contacts.…”