The susceptibility of disulfide bonds towards radiation damage may be explained by S...O interactions

• Main Authors: Rajasri Bhattacharyya, Jesmita Dhar, Shubhra Ghosh Dastidar, Pinak Chakrabarti, Manfred S. Weiss
• Format: Article
• Language: English
• Published: International Union of Crystallography 2020-09-01
• Series: IUCrJ
• Subjects: radiation damage; disulfide bonds; s...o interactions; quantum-chemical calculations; nbo; electron transfer
• Online Access: http://scripts.iucr.org/cgi-bin/paper?S2052252520008520

Radiation-induced damage to protein crystals during X-ray diffraction data collection is a major impediment to obtaining accurate structural information on macromolecules. Some of the specific impairments that are inflicted upon highly brilliant X-ray irradiation are metal-ion reduction, disulfide-bond cleavage and a loss of the integrity of the carboxyl groups of acidic residues. With respect to disulfide-bond reduction, previous results have indicated that not all disulfide bridges are equally susceptible to damage. A careful analysis of the chemical environment of disulfide bonds in the structures of elastase, lysozyme, acetylcholinesterase and other proteins suggests that S—S bonds which engage in a close contact with a carbonyl O atom along the extension of the S—S bond vector are more susceptible to reduction than the others. Such an arrangement predisposes electron transfer to occur from the O atom to the disulfide bond, leading to its reduction. The interaction between a nucleophile and an electrophile, akin to hydrogen bonding, stabilizes protein structures, but it also provides a pathway of electron transfer to the S—S bond, leading to its reduction during exposure of the protein crystal to an intense X-ray beam. An otherwise stabilizing interaction can thus be the cause of destabilization under the condition of radiation exposure.