Val119 has lower activity and thermal stability but increased affinity for endogenous substrates. Studies

suggest that heterozygosity for Val/Ile favors efficient isoaspartate repair. We have performed multiple molecular dynamics simulations of 119I and 119V PIMT. Both V119 and I119 interact with the same residues throughout all of the simulations. However, the larger Ile altered the orientations of alpha 5 and beta 5, both of which have co-substrate binding residues on their distal ends. I119 increases the flexibility of several residues, loosening up the S-adenosylmethionine (SAM)-binding site. These subtle changes are propagated towards the isoaspartate-docking site via residues common to both active sites. The increased mobility in 119I PIMT reorients alpha 3, resulting in a salt-bridge network at the substrate-binding interface that disrupts several key side-chain interactions in the isoaspartate site. LEE011 In contrast, 119V PIMT remains quite rigid with little change to the co-substrate binding site, which could hinder SAM’s binding Selleck PS341 and release, accounting for the decreased activity. These results shed light on the molecular basis behind the decreased activity and increased specificity for endogenous substrates

of 119V PIMT relative to the 119I variant. 119I PIMT catalyzes the methylation reaction but may have difficulties recognizing and orienting specific substrates due to its distorted substrate-binding site. Heterozygosity for both the Ile and Val alleles may provide the best of both worlds, allowing Fluocinolone acetonide the fast and specific methylation of damaged proteins.”
“The aim of the study was to extend the survival of adult spinal motor neurons in serum free culture. Anterior half of the spinal cord was removed from young

adult mice and dissociated. Cultured cells attempted to extend neurites within hours of incubation at 37 degrees C and died within 24 h. To prevent this early regenerative activity, thus to decrease the metabolic requirements of the neurons, cultures were transferred to 4 degrees C immediately after they were set and kept there for 3 days. Preparations were then taken to 37 degrees C where they lived up to 8 days. Some neurons continued to extend neurites until the day they died. To understand whether the enhancement of survival involves new protein synthesis, transcription and translation were blocked during cold pre-incubation, which shortened the half life of neurons but not changed the maximum survival period. In conclusion this study has shown that, in the serum-free cultures, the survival of adult spinal motor neurons can be significantly enhanced by cold pre-incubation whose effect seems to depend largely on a reduction in the metabolic activity and less on new protein synthesis. (c) 2012 Elsevier Ireland Ltd. All rights reserved.”
“The ORF3 protein of hepatitis E virus (HEV) is a multifunctional protein important for virus replication.