Showing papers by "Jon Clardy published in 1996"
TL;DR: The structure of the FRB domain of FRAP clarifies both rapamycin-independent and -dependent effects observed for mutants ofFRAP and its homologs in the family of proteins related to the ataxia-telangiectasia mutant gene product, and it illustrates how a small cell-permeable molecule can mediate protein dimerization.
Abstract: Rapamycin, a potent immunosuppressive agent, binds two proteins: the FK506-binding protein (FKBP12) and the FKBP-rapamycin-associated protein (FRAP). A crystal structure of the ternary complex of human FKBP12, rapamycin, and the FKBP12-rapamycin-binding (FRB) domain of human FRAP at a resolution of 2.7 angstroms revealed the two proteins bound together as a result of the ability of rapamycin to occupy two different hydrophobic binding pockets simultaneously. The structure shows extensive interactions between rapamycin and both proteins, but fewer interactions between the proteins. The structure of the FRB domain of FRAP clarifies both rapamycin-independent and -dependent effects observed for mutants of FRAP and its homologs in the family of proteins related to the ataxia-telangiectasia mutant gene product, and it illustrates how a small cell-permeable molecule can mediate protein dimerization.
855 citations
TL;DR: The chemical structure, regulation, and the target range of one of the antibiotics was determined as 3-amino-3-deoxy-D-glucose, also known as kanosamine, which was highly inhibitory to growth of plant-pathogenic oomycetes and moderately inhibitORY to certain fungi and inhibited few bacterial species tested.
Abstract: Bacillus cereus UW85 produces two antibiotics that contribute to its ability to suppress certain plant diseases (L. Silo-Suh, B. Lethbridge, S. J. Raffel, H. He, J. Clardy, and J. Handelsman, Appl. Environ. Microbiol. 60:2023-2030, 1994). To enhance the understanding of disease suppression by UW85, we determined the chemical structure, regulation, and the target range of one of the antibiotics. The antibiotic was identified as 3-amino-3-deoxy-D-glucose, also known as kanosamine. Kanosamine was highly inhibitory to growth of plant-pathogenic oomycetes and moderately inhibitory to certain fungi and inhibited few bacterial species tested. Maximum accumulation of kanosamine in B. cereus UW85 culture supernatants coincided with sporulation. Kanosamine accumulation was enhanced by the addition of ferric iron and suppressed by addition of phosphate to rich medium. Kanosamine accumulation was also enhanced more than 300% by the addition of alfalfa seedling exudate to minimal medium.
207 citations
173 citations
170 citations
TL;DR: In this article, two new caryophyllene sesquiterpenes have been isolated from Pestalotiopsis sp., an endophytic fungus associated with the bark and leaves of Taxus brevifolia.
Abstract: Two new caryophyllene sesquiterpenes have been isolated from Pestalotiopsis sp., an endophytic fungus associated with the bark and leaves of Taxus brevifolia. Pestalotiopsin A (1) has a novel oxatricyclic ring system while pestalotiopsin B (3) exists as two slowly equilibrating atropisomers (6:5 ratio of ββ:βα) in chloroform solution at room temperature. Structures of 1 and 3 were determined by spectroscopic analyses and single-crystal X-ray diffraction.
111 citations
Patent•
23 Oct 1996TL;DR: In this paper, a new crystalline composition comprising the ternary complex of rapamycin and FKBP12 was described, and its three dimensional structure in atomic detail.
Abstract: The invention relates to the human protein FRAP, and in particular to the FKBP12-rapamycin binding domain thereof and to the ternary complex formed by the FRB domain, rapamycin and FKBP12. A new crystalline composition comprising the ternary complex, coordinates defining its three dimensional structure in atomic detail, and uses thereof are disclosed.
57 citations
TL;DR: A sesquiterpene 2α-hydroxydimeninol 1 was isolated as the most polar metabolite produced by a cultured Pestalotiopsis sp., a fungus associated with Taxus sp.
Abstract: A new sesquiterpene 2α-hydroxydimeninol 1 was isolated as the most polar metabolite produced by a cultured Pestalotiopsis sp., a fungus associated with Taxus sp. Its structure was established by spectroscopic and X-ray diffraction analyses.
49 citations
TL;DR: The P13K SH3 domain, residues 1 to 85 of the P1 – 3 kinase p85 subunit, has been characterized by X-ray diffraction and solid-state interactions suggest a model of protein – protein aggregation that could be mediated by SH3 domains.
48 citations
TL;DR: A new tetracyclic diamine, (-) halicyclamine B (1), has been isolated from the sponge Xestospongia sp. and its structure was elucidated from NMR and X-ray crystallography data as discussed by the authors.
40 citations
TL;DR: Pyrrolosporin A is a new macrolide antitumor antibiotic possessing an unusual spiro-alpha-acyltetronic acid moiety and the structure was determined by a combination of NMR, MS, IR, UV, X-ray analysis and degradation studies.
Abstract: Pyrrolosporin A (1) is a new macrolide antitumor antibiotic possessing an unusual spiro-a-acyltetronic acid moiety. The antibiotic was isolated from the fermentation broth of Micromonospora sp. by vacuum liquid chromatography, crystallization and reversed phase HPLC (CIS). The structure was determined by a combination of NMR, MS, IR, UV, X-ray analysis and degradation studies.
33 citations
TL;DR: Analysis of the active-site residues of a fully functional chorismate mutase representing the N-terminal 113 amino acids of the Escherichia coli P-protein suggests that Lys39 and Gln88 play critical roles in catalyzing the rearrangement of chorISMate to prephenate.
TL;DR: In this paper, tridentatols A-C (1-3) with an uncommon sulfur-containing functional group have been isolated from the marine hydroid Tridentata marginata.
TL;DR: The overall structure and relative stereochemistry of ossamycin have now been determined by single crystal X-ray diffraction studies, and absolute stereochemistry was established according to the previously determined configuration of its aminosaccharide constituent, ossamine.
Abstract: Ossamycin is a cytotoxic agent of undetermined structure that was originally isolated in 1965 from culture broths of Streptomyces hygroscopicus var. ossamyceticus. Its overall structure and relative stereochemistry have now been determined by single crystal X-ray diffraction studies. Absolute stereochemistry was established according to the previously determined configuration of its aminosaccharide constituent, ossamine. The aglycone of ossamycin possesses a 24-membered macrolide ring system onto which is incorporated both a 6,6-spiroketal and 5-membered hemiketal ring system. The overall three-dimensional structure possesses features in common with the related macrocyclic antibiotics dunaimycin, cytovaricin, and A82548A.
TL;DR: In this paper, the structures of the new compounds were determined by spectral and chemical methods, and the absolute stereochemistries of volutamides B and C were established by CD measurements.
TL;DR: In this article, the chalcone-epoxide was treated with lithium tetramethylpiperidide (LTE) to yield enolate and remote anions, which upon formation, added to the starting material to yield diastereoisomeric products.
TL;DR: In this article, two new caryophyllene sesquiterpenes have been isolated from Pestalotiopsis sp., an endophytic fungus associated with the bark and leaves of Taxus brevifolia.
Abstract: Two new caryophyllene sesquiterpenes have been isolated from Pestalotiopsis sp., an endophytic fungus associated with the bark and leaves of Taxus brevifolia. Pestalotiopsin A (1) has a novel oxatricyclic ring system while pestalotiopsin B (3) exists as two slowly equilibrating atropisomers (6:5 ratio of ββ:βα) in chloroform solution at room temperature. Structures of 1 and 3 were determined by spectroscopic analyses and single-crystal X-ray diffraction.
TL;DR: In this paper, the structures of the new compounds were determined by spectral and chemical methods, and the absolute stereochemistries of volutamides B and C were established by CD measurements.
Abstract: Volutamides A-E (1–5), halogenated alkaloids of amino acid origin, have been isolated from the temperate Atlantic bryozoan Amathia convoluta Lamouroux. The structures of the new compounds were determined by spectral and chemical methods. The absolute stereochemistries of volutamides B and C were established by CD measurements, while the absolute stereochemistries of volutamides D and E could not be established with confidence. Several of the volutamides deterred feeding by potential predators and were toxic toward larvae of a co-occurring hydroid, suggesting that these metabolites form the basis of an effective chemical defense.