Getting protein solvent structures down cold

摘要

At the heart of biochemistry are molecular interactions with solvent and hydrogen bonds. Yet, experimental placement of hydrogen atoms is supported only in a limited number of cases with x-ray crystallography, the preeminent technique providing atomic resolution molecular models for proteins 40 kDa and larger. This lack of experimental evidence leads to ambiguity in explication of enzymatic mechanisms and uncertain fits when trying to match ligand-binding sites. It is the experimental determination of hydrogen atom position, especially labile hydrogens, that is fueling the resurgence of neutron protein crystallography (1-3). Newly commissioned and planned facilities, combined with improved detectors and the use of a broader spectrum of available neutrons, are increasing the number of structural problems that can be solved with neutron diffraction (4-6), In this issue of PNAS, Matthew Blakeley, Joseph Kalb (Gilboa), and John Helliwell collaborate with Dean Myles to extend the group's previous x-ray and room-tempcraturc neutron diffraction studies (1, 7) of the jack bean protein, Con A, with a low-temperature neutron diffraction study completed by using the quasi-Laue dif-fractometer (LADI) at the Institut Laue-Langevin (ILL) in Grenoble, France (8). The outcome of this research is a further extension of the range of protein crystallographic problems addressable with neutron diffraction.