Unfolded states under folding conditions accommodate sequence-specific conformational preferences with random coil-like dimensions

Proteins are marginally stable molecules that fluctuate between folded and unfolded states. Here, we provide a high-resolution description of unfolded states under refolding conditions for the N-terminal domain of the L9 protein (NTL9). We use a combination of time-resolved Förster resonance energy transfer (FRET) based on multiple pairs of minimally perturbing labels, time-resolved small-angle X-ray scattering (SAXS), all-atom simulations, and polymer theory. Upon dilution from high denaturant, the unfolded state undergoes rapid contraction. Although this contraction occurs before the folding transition, the unfolded state remains considerably more expanded than the folded state and accommodates a range of local and nonlocal contacts, including secondary structures and native and nonnative interactions. Paradoxically, despite discernible sequence-specific conformational preferences, the ensemble-averaged properties of unfolded states are consistent with those of canonical random coils, namely polymers in indifferent (theta) solvents. These findings are concordant with theoretical predictions based on coarse-grained models and inferences drawn from single-molecule experiments regarding the sequence-specific scaling behavior of unfolded proteins under folding conditions

βα-Hairpin Clamps Brace βαβ Modules and Can Make Substantive Contributions to the Stability of TIM Barrel Proteins

Non-local hydrogen bonding interactions between main chain amide hydrogen atoms and polar side chain acceptors that bracket consecutive βα or αβ elements of secondary structure in αTS from E. coli, a TIM barrel protein, have previously been found to contribute 4–6 kcal mol−1 to the stability of the native conformation. Experimental analysis of similar βα-hairpin clamps in a homologous pair of TIM barrel proteins of low sequence identity, IGPS from S. solfataricus and E. coli, reveals that this dramatic enhancement of stability is not unique to αTS. A survey of 71 TIM barrel proteins demonstrates a 4-fold symmetry for the placement of βα-hairpin clamps, bracing the fundamental βαβ building block and defining its register in the (βα)8 motif. The preferred sequences and locations of βα-hairpin clamps will enhance structure prediction algorithms and provide a strategy for engineering stability in TIM barrel proteins

Cytotoxic activity and essential oil composition of leaves and berries of Juniperus excelsa

The composition of the water-distilled essential oils of the berries and leaves of Juniperus excelsa M. Bieb. were analyzed by gas chromatography-mass spectrometry (GCMS). The main components in the berries of J. excelsa, accounting for 56.1% of the oil, were determined as alpha-pinene (34.0%), cedrol (12.3%), L-verbenol (5.4%), and D-verbenol (4.4%) while in the leaves of J. excelsa, accounting for 63.2% of the oil, were found to be alpha-pinen (29.7%), cedrol (25.3%), alpha-muurolene (4.4%), and 3-carene (3.8%). Cytotoxic and antimicrobial potential of the berries and leaves of J. excelsa were investigated

Late onset Pott's paraplegia

Background: Pott's disease may cause late neurological involvement due to development of sharp kyphosis. Anterior decompression and fusion is the treatment of choice for this disorder