Project description:The objective of this project was to characterize the salivary proteome of patients with recurrent aphthous stomatitis using mass spectrometry-based proteomics(nLC-MS/MS) and assess its clinical usefulness in identifying the most representative biological and molecular processes during the course of lesions. To do this, we conducted a case-control study, analyzing the saliva of healthy controls and patients with recurrent aphthous stomatitis during a complete ulcerative cycle (active ulcers and absence of lesions).
Project description:Integrated analysis of MLL-AF9 AML patients and model leukemias highlights RET and other novel therapeutic targets [RNA-Seq_normal]
Project description:Integrated analysis of MLL-AF9 AML patients and model leukemias highlights RET and other novel therapeutic targets (Leukemia Cell Bank)
Project description:Kynureninase is a member of a large family of catalytically diverse but structurally homologous pyridoxal 5'-phosphate (PLP) dependent enzymes known as the aspartate aminotransferase superfamily or alpha-family. The Homo sapiens and other eukaryotic constitutive kynureninases preferentially catalyze the hydrolytic cleavage of 3-hydroxy-l-kynurenine to produce 3-hydroxyanthranilate and l-alanine, while l-kynurenine is the substrate of many prokaryotic inducible kynureninases. The human enzyme was cloned with an N-terminal hexahistidine tag, expressed, and purified from a bacterial expression system using Ni metal ion affinity chromatography. Kinetic characterization of the recombinant enzyme reveals classic Michaelis-Menten behavior, with a Km of 28.3 +/- 1.9 microM and a specific activity of 1.75 micromol min-1 mg-1 for 3-hydroxy-dl-kynurenine. Crystals of recombinant kynureninase that diffracted to 2.0 A were obtained, and the atomic structure of the PLP-bound holoenzyme was determined by molecular replacement using the Pseudomonas fluorescens kynureninase structure (PDB entry 1qz9) as the phasing model. A structural superposition with the P. fluorescens kynureninase revealed that these two structures resemble the "open" and "closed" conformations of aspartate aminotransferase. The comparison illustrates the dynamic nature of these proteins' small domains and reveals a role for Arg-434 similar to its role in other AAT alpha-family members. Docking of 3-hydroxy-l-kynurenine into the human kynureninase active site suggests that Asn-333 and His-102 are involved in substrate binding and molecular discrimination between inducible and constitutive kynureninase substrates.
Project description:Integrated analysis of MLL-AF9 AML patients and model leukemias highlights RET and other novel therapeutic targets (RNA-seq AML development)