Formation and structure of the ferryl [Fe[double bond, length as m-dash]O] intermediate in the non-haem iron halogenase SyrB2: classical and QM/MM modelling agree.

To rationalise mechanistically the intriguing regio- and chemoselectivity patterns for different substrates of the non-haem iron/2-oxoglutarate dependent halogenase SyrB2, it is crucial to elucidate the structure of the pivotal [FeIV[double bond, length as m-dash]O] intermediate. We have approached the problem by a combination of classical and QM/MM modelling. We present complete atomistic models of SyrB2 in complex with its native substrate l-threonine as well as l-α-amino butyric acid and l-norvaline (all conjugated to the pantetheine tether), constructed by molecular docking and extensive MD simulations. We evaluate five isomers of the [Fe[double bond, length as m-dash]O] intermediate in these simulations, with a view to identifying likely structures based on a simple "reaction distance" measure. Starting from models of the resting state, we then use QM/MM calculations to investigate the formation of the [Fe[double bond, length as m-dash]O] species for all three substrates, identifying the intermediates along the O2 activation/decarboxylation pathway on the S = 1, 2, and 3 potential-energy surfaces. We find that, despite differences in the detailed course of the reaction, essentially all pathways produce the same [Fe[double bond, length as m-dash]O] structure, in which the oxido is directed away from the substrate.

Inferring handedness from lithic evidence.

Until recently research into the origins of human handedness has been hampered by the lack of valid techniques for inferring handedness in pre-modern populations. A method developed by Toth for inferring handedness from lithic evidence, based on orientation of the cortex on lithic flakes, has produced promising results. However, this method is limited in applicability and has a variable signal to noise ratio. The authors describe a separate method, based on the orientation of the cone of percussion in lithic flakes, for inferring handedness from the lithic evidence. This method complements the cortex method. Some preliminary experimental evidence is presented which indicates that handedness can be inferred from lithic evidence using the cone of percussion method. Suggestions for further research are made.