Joseph L. Kim

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The X-ray structure of the ternary complex of a calcineurin A fragment, calcineurin B, FKBP12, and the immunosuppressant drug FK506 (also known as tacrolimus) has been determined at 2.5 A resolution, providing a description of how FK506 functions at the atomic level. In the structure, the FKBP12-FK506 binary complex does not contact the phosphatase active(More)
BACKGROUND Hepatitis C virus (HCV) represents a major health concern as it is responsible for a significant number of hepatitis cases worldwide. Much research has focused on the replicative enzymes of HCV as possible targets for more effective therapeutic agents. HCV NS3 helicase may provide one such suitable target. Helicases are enzymes which can unwind(More)
The three-dimensional structure of a TATA-box binding polypeptide complexed with the TATA element of the adenovirus major late promoter has been determined by X-ray crystallography at 2.25 A resolution. Binding of the saddle-shaped protein induces a conformational change in the DNA, inducing sharp kinks at either end of the sequence TATAAAAG. Between the(More)
Human cancer genomes harbour a variety of alterations leading to the deregulation of key pathways in tumour cells. The genomic characterization of tumours has uncovered numerous genes recurrently mutated, deleted or amplified, but gene fusions have not been characterized as extensively. Here we develop heuristics for reliably detecting gene fusion events in(More)
Cocrystal structures of wild-type TATA box-binding protein (TBP) recognizing 10 naturally occurring TATA elements have been determined at 2.3-1.8 A resolution, and compared with our 1.9 A resolution structure of TBP bound to the Adenovirus major late promoter (AdMLP) TATA box (5'-TATAAAAG-3'). Minor-groove recognition by the saddle-shaped protein induces(More)
Raf inhibitors are under clinical investigation, specifically in patients with tumor types harboring frequent activating mutations in B-Raf. Here, we show that cell lines and tumors harboring mutant B-Raf were sensitive to a novel series of Raf inhibitors (e.g., (V600E)B-Raf A375, IC(50) on cells = 2 nmol/L; ED(50) on tumor xenografts = 1.3 mg/kg). However,(More)
Hepatitis C Virus helicase activity has been mapped to the COOH-terminal 450 residues of the NS3 protein. Due to its complexity and presumed essentiality for viral replication, the helicase is an attractive target for drug discovery. The elucidation of the atomic structure of the HCV NS3 helicase in complex with oligonucleotide and with ADP has helped(More)
An estimated 1% of the global human population is infected by hepatitis C viruses (HCVs), and there are no broadly effective treatments for the debilitating progression of chronic hepatitis C. A serine protease located within the HCV NS3 protein processes the viral polyprotein at four specific sites and is considered essential for replication. Thus, it(More)
Inhibition of angiogenesis is a promising and clinically validated approach for limiting tumor growth and survival. The receptor tyrosine kinase Tie-2 is expressed almost exclusively in the vascular endothelium and is required for developmental angiogenesis and vessel maturation. However, the significance of Tie-2 signaling in tumor angiogenesis is not well(More)
The three-dimensional structure of a TATA box-binding protein (TBP) from Arabidopsis thaliana complexed with a fourteen base pair oligonucleotide bearing the Adenovirus major late promoter TATA element has been refined at 1.9 A resolution, giving a final crystallographic R-factor of 19.4%. Binding of the monomeric, saddle-shaped alpha/beta protein induces(More)