Role of Asn(2) and Glu(7) residues in the oxidative folding and on the conformation of the N-terminal loop of apamin.

The X-ray structure of [N-acetyl]-apamin has been solved at 0.95 A resolution. It consists of an 1-7 N-terminal loop stabilized by an Asn-beta-turn motif (2-5 residues) and a helical structure spanning the 9-18 residues tightly linked together by two disulfide bonds. However, neither this accurate X-ray nor the available solution structures allowed us to rationally explain the unusual downfield shifts observed for the Asn(2) and Glu(7) amide signals upon Glu(7) carboxylic group ionization. Thus, apamin and its [N-acetyl], [Glu(7)Gln], [Glu(7)Asp], and [Asn(2)Abu] analogues and submitted to NMR structural studies as a function of pH. We first demonstrated that the Glu(7) carboxylate group is responsible for the large downfield shifts of the Asn(2) and Glu(7) amide signals. Then, molecular dynamics simulations suggested unexpected interactions between the carboxylate group and the Asn(2) and Glu(7) amide protons as well as the N-terminal alpha-amino group, through subtle conformational changes that do not alter the global fold of apamin. In addition, a structural study of the [Asn(2)Abu] analogue, revealed an essential role of Asn(2) in the beta-turn stability and the cis/trans isomerization of the Ala(5)-Pro(6) amide bond. Interestingly, this proline isomerization was shown to also depend on the ionization state of the Glu(7) carboxyl group. However, neither destabilization of the beta-turn nor proline isomerization drastically altered the helical structure that contains the residues essential for binding. Altogether, the Asn(2) and Glu(7) residues appeared essential for the N-terminal loop conformation and thus for the selective formation of the native disulfide bonds but not for the activity. (c) 2007 Wiley Periodicals, Inc. Biopolymers, 2007

Analyzing Mental Health Diseases in a Spanish Region Using Software Based on Graph Theory Algorithms

International audienceAt present, network analysis based on the graph theory has become a widely used technique in the field of Mental Health. The networks are part of the main structure of BeGraph software, a 3D visualization cloud application that allows the analysis of complex networks. The main objective of this study is to analyze, through the BeGraph software, the behavior of Mental Health prevalent diseases in a region of Spain, in order to make health decisions. The study used a database with a total of 9403 patient’s records with Mental Health diseases, which belong to two hospitals in Castilla and Leon, Spain, and the 3D visualization software, BeGraph. The results obtained allow us to determine the main diseases detected in each hospital included in the study 6.5% of admissions from the University Clinic of Valladolid with unspecified paranoid schizophrenia and 8.84% of admissions from Rio Hortega Hospital with dysthymic disorder. The analysis of the data allows us to focus on the Mental Health main pathologies detected in the hospitals evaluated, and propose prediction algorithms that help in their diagnosis and treatment. © 2021, Springer Nature Singapore Pte Ltd

Autonomic effects of some scorpion venoms and toxins

10.1046/j.1440-1681.2002.03726.xClinical and Experimental Pharmacology and Physiology299795-801CEXP