OBJECTIVE: There is a large literature linking current BMI to levels of cardiovascular risk biomarkers, but it is unknown whether measures of BMI earlier in the life course and maximum BMI are predictive of current levels of biomarkers. The objective of the current study was to determine how current, maximum and age-25 BMI among individuals over the age of 60 years are associated with their current levels of cardiovascular risk biomarkers. DESIGN: Cross-sectional study with retrospective recall. SETTING: Costa Rica (n 821) and the USA (n 4110). SUBJECTS: Nationally representative samples of adults aged 60 years or over. RESULTS: We used regression models to examine the relationship between multiple meaures of BMI with four established cardiovascular risk biomarkers. The most consistent predictor of current levels of systolic blood pressure, TAG and HDL-cholesterol was current BMI. However, maximum BMI was the strongest predictor of glycosylated Hb (HbA1c) and was also related to HDL-cholesterol and TAG. HbA1c was independent of current BMI. We found that these relationships are consistent between Costa Rica and the USA for HbA1c and for HDL-cholesterol. CONCLUSIONS: Current levels of cardiovascular risk biomarkers are not only the product of current levels of BMI, but also of maximum lifetime BMI, particularly for levels of HbA1c and for HDL-cholesterol. Managing maximum obtained BMI over the life course may be most critical for maintaining the healthiest levels of cardiovascular risk.

Many species of Gram-positive bacteria use sortase transpeptidases to covalently affix proteins to their cell wall or to assemble pili. Sortase-displayed proteins perform critical and diverse functions for cell survival, including cell adhesion, nutrient acquisition, and morphological development, among others. Based on their amino acid sequences, there are at least six types of sortases (class A to F enzymes); however, class E enzymes have not been extensively studied. Class E sortases are used by soil and freshwater-dwelling Actinobacteria to display proteins that contain a non-canonical LAXTG sorting signal, which differs from 90% of known sorting signals by substitution of alanine for proline. Here we report the first crystal structure of a class E sortase, the 1.93 Å resolution structure of the SrtE1 enzyme from Streptomyces coelicolor. The active site is bound to a tripeptide, providing insight into the mechanism of substrate binding. SrtE1 possesses β3/β4 and β6/β7 active site loops that contact the LAXTG substrate and are structurally distinct from other classes. We propose that SrtE1 and other class E sortases employ a conserved tyrosine residue within their β3/β4 loop to recognize the amide nitrogen of alanine at position P3 of the sorting signal through a hydrogen bond, as seen here. Incapability of hydrogen-bonding with canonical proline-containing sorting signals likely contributes to class E substrate specificity. Furthermore, we demonstrate that surface anchoring of proteins involved in aerial hyphae formation requires an N-terminal segment in SrtE1 that is presumably positioned within the cytoplasm. Combined, our results reveal unique features within class E enzymes that enable them to recognize distinct sorting signals, and could facilitate the development of substrate-based inhibitors of this important enzyme family.