Iron–sulfur protein folds,iron–sulfur chemistry,and evolution

An inventory of unique local protein folds around Fe–S clusters has been derived from the analysis of protein structure databases. Nearly 50 such folds have been identified, and over 90% of them harbor low-potential [2Fe–2S]^2+,+ or [4Fe–4S]^2+,+ clusters. In contrast, high-potential Fe–S clusters, notwithstanding their structural diversity, occur in only three different protein folds. These observations suggest that the extant population of Fe–S protein folds has to a large extent been shaped in the reducing iron- and sulfur-rich environment that is believed to have predominated on this planet until approximately two billion years ago. High-potential active sites are then surmised to be rarer because they emerged later, in a more oxidizing biosphere, in conditions where iron and sulfide had become poorly available, Fe–S clusters were less stable, and in addition faced competition from heme iron and copper active sites. Among the low-potential Fe–S active sites, protein folds hosting [4Fe–4S]^2+,+ clusters outnumber those with [2Fe–2S]^2+,+ ones by a factor of 3 at least. This is in keeping with the higher chemical stability and versatility of the tetranuclear clusters, compared with the binuclear ones. It is therefore suggested that, at least while novel Fe–S sites are evolving within proteins, the intrinsic chemical stability of the inorganic moiety may be more important than the stabilizing effect of the polypeptide chain. The discovery rate of novel Fe–S-containing protein folds underwent a sharp increase around 1995, and has remained stable to this day. The current trend suggests that the mapping of the Fe–S fold space is not near completion, in agreement with predictions made for protein folds in general. Altogether, the data collected and analyzed here suggest that the extant structural landscape of Fe–S proteins has been shaped to a large extent by primeval geochemical conditions on one hand, and iron–sulfur chemistry on the other.     

Calculation of the Three-Dimensional Structures of Two Antigenic Sequences, Pro–Pro–Pro–Pro–Asn–Pro–Asn–Asp–Pro and Pro–Pro–Pro–Pro–Asn–Pro–Asn–Asp–Pro–Pro–Pro, of the Circumsporozoite Protein From a Malaria-Causing Plasmodium

Using the chain build-up procedure based on the program ECEPP, we have computed the lowest energy structures for two terminally blocked subsequences from the antigenic circumsporozoite protein of Plasmodium berghei, that is known to cause malaria in animals. The full antigenic sequence is an octapeptide proline-rich tandem repeat, (Pro–Pro–Pro–Pro–Asn–Pro–Asn–Asp)₂. We computed the structures for the first octapeptide plus one Pro from the second octapeptide, terminally blocked CH₃CO–Pro–Pro–Pro–Pro–Asn–Pro–Asn–Asp–Pro–NHCH₃ as well as the first octpeptide with an additional three Pro residues from the adjoining unit, i.e., CH₃CO–Pro–Pro–Pro–Pro–Asn–Pro–Asn–Asp–Pro–Pro–Pro–NHCH₃. We find that the first sequence adopts a number of different low energy structures, the most probable of which has a probability of occurrence of 56 %. Addition of two more Pro residues results in the adoption a single, unique lowest energy structure that has a probability of occurrence of over 95 % without solvation effects and 86 % when solvation effects are included in the calculations. We predict that this structure may be the one recognized as a major antigenic determinant.     

Phase Behavior, Stability, and Mesomorphism of Monostearin–oil–water Gels

This paper is the characterization of a new material comprised of oil, water, monostearin and stearic acid, which can be used as a heart-friendly, low-saturate, trans fatty acid-free spreadable fat and shortening. Oil–water–monstearin mixtures formed a gel above 2% monostearin and 30% water and were stable over a month’s time. An increase in the storage modulus (G′), and peak melting temperature (T _m) was observed over time, which suggests a slow change in structure to a more solid form. Powder x-ray diffraction measurements at temperatures above the Krafft temperature of the monglyceride (57°C) indicated the existence of a lamellar liquid crystalline phase $ {\left( {L_{\alpha } } \right)} This paper is the characterization of a new material comprised of oil, water, monostearin and stearic acid, which can be used as a heart-friendly, low-saturate, trans fatty acid-free spreadable fat and shortening. Oil–water–monstearin mixtures formed a gel above 2% monostearin and 30% water and were stable over a month’s time. An increase in the storage modulus (G′), and peak melting temperature (T _m) was observed over time, which suggests a slow change in structure to a more solid form. Powder x-ray diffraction measurements at temperatures above the Krafft temperature of the monglyceride (57°C) indicated the existence of a lamellar liquid crystalline phase with a (001) reflection occurring at 50 ?. In addition to the 50 ? reflection at small angles, a wide angle reflection at 4.2 ? was observed upon cooling below 60°C, indicating a transition from the to the phase, which upon storage at 22°C for one day converted to the coagel, or β-gel phase.     

Miospore assemblages from the Silurian–Devonian boundary,in borehole A1-61, Ghadamis Basin,Libya

Well preserved and diversified miospore assemblages have been recorded from a relatively continuous sequence in borehole A1-61 which spans the Silurian–Devonian boundary in the northwestern part of the Ghadamis Basin, Libya. The sequence is represented by early Devonian Lochkovian beds of the Tadrart Formation that transgress onto the Silurian Ludlow-Pridoli beds of the upper part of the ‘Alternances Argilo-gréseuses’ Formation. The present work demonstrates a succession of miospore assemblages from closely sampled layers that have been stratigraphically dated as Ludlow–middle Pridoli and early Lochkovian by chitinozoans and acritarchs. Over 80 species of cryptospores and trilete spores have been identified. Modified detailed morphological interpretations are given. The miospore assemblages are correlated with miospore zonation schemes established for the type sequences of the Welsh Borderland, and those previously described from Libya. Early occurrences of some species as Streelispora newportensis on the western Gondwana plate, are put forward by comparison with the Old Red Sandstone continent. Phytogeographic and palaeobotanic implications based on these observations are discussed.     

Novel anti-viability ceramide analogs: Design,synthesis, and structure–activity relationship studies of substituted (S)-2-(benzylideneamino)-3-hydroxy-N-tetradecylpropanamides

A group of novel l-serinamides, substituted (S)-2-(benzylideneamino)-3-hydroxy-N-tetradecylpropanamides (3a–o) and substituted (S)-2-(benzylamino)-3-hydroxy-N-tetradecyl propanamides (4c, 4i, 4l, and 4o), were synthesized as potential anti-tumor lead compounds. In vitro cell viability assay results indicate treatment with 3a–o compounds resulted in significant inhibition of cell viability in the chemoresistant breast cancer cell line, MCF-7TN-R. Compounds 3i and 3l, both ortho-substituted analogs, show the greatest efficacy with IC₅₀ values of 10.3 μM and 12.5 μM, respectively. The SAR analysis indicate that the imine functional group of 3a–o is critical for the cellular anti-viability effect, and the partial atomic charge (PAC) value of imine C atom is a valuable structural parameter for predicting the activity of these ceramide analogs.     

Grandmothering in Cambridgeshire, 1770–1861

The effects of grandparent survival on child survival and mean interbirth interval, both independent of and relative to parent survival, were investigated in a historical population. Families for the data set were reconstituted from the parish and census records of Cambridgeshire, 1770–1861. In a logistic regression analysis, only the mother’s and the maternal grandmother’s survival were found to be significant predictors of child survival. Maternal grandmother’s survival was found to influence child survival both via maternal survival and independent of maternal survival. Grandparent survival was not found to influence mean interbirth interval. These findings are reviewed with respect to other studies of grandmothering, the Grandmother Hypothesis, and the evolutionary significance of human female postreproductive lifespan. Gillian Ragsdale is a postgraduate student at the Leverhulme Centre for Human Evolution Studies (LCHES), Cambridge University, UK, currently investigating the evolution of human social cognition. She was originally a molecular geneticist, and subsisted through the intervening years in educational publishing.