Publications by authors named "A Sosa-Peinado"
Article Synopsis
- PTP1B (protein tyrosine phosphatase 1B) is a key enzyme involved in insulin and leptin sensitivity, playing a significant role in metabolism, type 2 diabetes, and obesity.
- There are four main strategies to inhibit PTP1B: orthosteric, allosteric, bidentate inhibition, and PTPN1 gene silencing, but creating effective inhibitors is difficult due to the enzyme's widespread presence and complex structure.
- The article reviews advances in PTP1B research since its discovery in 1988 and discusses its role in metabolic diseases along with the ongoing challenges in developing selective and effective inhibitors.
Substrate-binding proteins (SBPs) are used by organisms from the three domains of life for transport and signalling. SBPs are composed of two domains that collectively trap ligands with high affinity and selectivity. To explore the role of the domains and the integrity of the hinge region between them in the function and conformation of SBPs, here, we describe the ligand binding, conformational stability and folding kinetics of the Lysine Arginine Ornithine (LAO) binding protein from Salmonella thiphimurium and constructs corresponding to its two independent domains.
View Article and Find Full Text PDFIn the present study, we reported the interactions at the molecular level of a series of compounds called Bisindolylmaleimide, as potential inhibitors of the calmodulin protein. Bisindolylmaleimide compounds are drug prototypes derived from , an alkaloid with activity for cancer treatment. Bisindolylmaleimide compounds II, IV, VII, X, and XI, are proposed and reported as possible inhibitors of calmodulin protein for the first time.
View Article and Find Full Text PDFWe study the CaM-peptide interactions for four CaM-related peptides with different calcium equivalents, using the CaM-M124C- biosensor and Molecular Dynamics (MD). Due to the high sensitivity of the biosensor, we were able to calculate five based on the number of calcium equivalents for each peptide, showing a directly proportional relationship between the degree of calcium saturation and the increased affinity for the Calspermin, nNOS, and skMLSK peptides; while the CaV1.1 peptide has a degree of affinity independent of the number of calcium equivalent.
View Article and Find Full Text PDFArticle Synopsis
- Understanding binding thermodynamics is important for studying how molecular complexes gain affinity and selectivity, particularly in periplasmic binding proteins (PBPs), which are used in biosensor design.
- The lysine-arginine-ornithine binding protein (LAO) has a significant difference in affinity for l-arginine and l-histidine, attributed to various protein-ligand contacts and enthalpic factors.
- Structural analysis through alanine scanning, isothermal titration calorimetry, and X-ray crystallography reveals that multiple residues influence selectivity and affinity, while solvent effects also play a crucial role in binding thermodynamics.