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FK506-binding protein 52 (FKBP52), which binds FK506 and possesses peptidylprolyl isomerase activity, is an important immunophilin involved in the heterocomplex of steroid receptors with heat-shock protein 90. Here we report the crystal structures of two overlapped fragments [N(1-260) and C(145-459)] of FKBP52 and the complex with a C-terminal pentapeptide(More)
Structure-function studies have analyzed substitutions within the glucagon-like peptide-1 (GLP-1) sequence that increase resistance to proteolysis, however, the investigation into how such substitutions alter interactions at the GLP-1 receptor (GLP-1R) has captured less attention. This work describes our efforts at identifying relevant interactions between(More)
OBJECTIVE Fibroblast activation protein (FAP) is a serine protease belonging to a S9B prolyl oligopeptidase subfamily. This enzyme has been implicated in cancer development and recently reported to regulate degradation of FGF21, a potent metabolic hormone. Using a known FAP inhibitor, talabostat (TB), we explored the impact of FAP inhibition on metabolic(More)
Glucagon and glucagon-like peptide-1 (GLP-1)are two structurally related hormones that acutely regulate glucose control in opposite directions through homologous receptors. The molecular basis for selectivity between these two hormones and their receptors is of physiological and medicinal importance. The application of co-agonists to enhance body weight(More)
Based on the structure of FKBP12 complexed with FK506 or rapamycin, with computer-aided design, two neurotrophic ligands, (3R)-4-(p-Toluenesulfonyl)-1,4-thiazane-3-carboxylic acid-L-Leucine ethyl ester and (3R)-4-(p-Toluenesulfonyl)-1,4-thiazane-3-carboxylic acid-L-phenylalanine benzyl ester, were designed and synthesized. Fluorescence experiments were used(More)
Insulin degrading enzyme (IDE), a zinc metalloprotease, can specifically recognize and degrade insulin, as well as several amyloidogenic peptides such as amyloid beta (Abeta) and amylin. The disruption of IDE function in rodents leads to glucose intolerance and cerebral Abeta accumulation, hallmarks of type 2 diabetes and Alzheimer's disease, respectively.(More)
A novel neurotrophic ligand, (3R)-4-(p-Toluenesulfonyl)-1,4-thiazane-3-carboxylic acid-L-Leucine ethyl ester, has been complexed with FKBP12 and crystallized using the hanging-drop vapor-diffusion method. Crystals belong to P2(1) space group, with unit cell parameters a=41.2, b=29.6, c=41.5 A, beta=114.0 degrees. The crystals diffract to 1.8 A resolution(More)
Glucagon and glucagon-like peptide 1 (GLP-1) are drugs or drug candidates for the treatment of metabolic diseases such as diabetes and obesity. The native hormones have pharmacological deficiencies such as short half-life and poor solubility. A novel glucagon receptor agonist named glucagon-Cex has been designed, synthesized and crystallized. This peptide(More)
FKBP52 is a member of the FK506-binding protein family (FKBPs). The N-terminal domain of FKBP52 (FKBP52-N; residues 1-140) is responsible for peptidyl-prolyl isomerase activity and binding of FK506. Here, the crystal structure of FKBP52-N has been determined by molecular replacement to 2.4 A. FKBP52-N is defined by a six-stranded antiparallel beta-sheet(More)
FKBP52 is a high-molecular-weight immunophilin belonging to the FKBP (FK506-binding protein) family. FKBP52 is one of several chaperone proteins associated with untransformed steroid receptors in steroid receptor-hsp90 heterocomplexes. Here, the C-terminal domain (amino acids 145-459) has been cloned, overexpressed and purified. Crystals were obtained using(More)