Abstract:
The present invention provides crystals of a Staphylococcus aureus DnaG primase and Escherichia coli DnaG primase proteins complexed with ligands. The three-dimensional structural information for Staphylococcus aureus DnaG primase with magnesium bound, Staphylococcus aureus DnaG primase with sulfate bound, and Escherichia coli DnaG primase with manganese bound is provided. The present invention provides procedures for identifying agents that can inhibit the cell growth of Staphylococcus aureus, Escherichia coli , or both through the use of rational drug design utilizing the crystallographic data.
Abstract:
The present invention provides crystals of a topoisomerase polypeptide and a nucleic acid. The crystals are of use in elucidating the structure of topoisomerase-nucleic acid complexes. Moreover, the crystals are of use in the discovery of ligands that interact with topoisomerase- nucleic acid complexes and modulate the activity of such complexes through this interaction.
Abstract:
The use of microfluidic structures enables high throughput screening of protein crystallization. In one embodiment, an integrated combinatoric mixing chip allows for precise metering of reagents to rapidly create a large number of potential crystallization conditions, with possible crystal formations observed on chip. In an alternative embodiment, the microfluidic structures may be utilized to explore phase space conditions of a particular protein crystallizing agent combination, thereby identifying promising conditions and allowing for subsequent focused attempts to obtain crystal growth.
Abstract:
The present invention provides crystals of a topoisomerase polypeptide and a nucleic acid. The crystals are of use in elucidating the structure of topoisomerase-nucleic acid complexes. Moreover, the crystals are of use in the discovery of ligands that interact with topoisomerase- nucleic acid complexes and modulate the activity of such complexes through this interaction.
Abstract:
The present invention relates to microfluidic devices and methods facilitating the growth and analysis of crystallized materials such as proteins. In accordance with one embodiment, a crystal growth architecture is separated by a permeable membrane from an adjacent well having a much larger volume. The well may be configured to contain a fluid having an identity and concentration similar to the solvent and crystallizing agent employed in crystal growth, with diffusion across the membrane stabilizing that process. Alternatively, the well may be configured to contain a fluid having an identity calculated to affect the crystallization process. In accordance with the still other embodiment, the well may be configured to contain a material such as a cryo-protectant, which is useful in protecting the crystalline material once formed.
Abstract:
The present invention relates to microfluidic devices and methods facilitating the growth and analysis of crystallized materials such as proteins. In accordance with one embodiment, a crystal growth architecture is separated by a permeable membrane from an adjacent well having a much larger volume. The well may be configured to contain a fluid having an identity and concentration similar to the solvent and crystallizing agent employed in crystal growth, with diffusion across the membrane stabilizing that process. Alternatively, the well may be configured to contain a fluid having an identity calculated to affect the crystallization process. In accordance with the still other embodiment, the well may be configured to contain a material such as a cryo-protectant, which is useful in protecting the crystalline material once formed.
Abstract:
The present invention provides crystals of a Staphylococcus aureus DnaG primase and Escherichia coli DnaG primase proteins complexed with ligands. The three-dimensional structural information for Staphylococcus aureus DnaG primase with magnesium bound, Staphylococcus aureus DnaG primase with sulfate bound, and Escherichia coli DnaG primase with manganese bound is provided. The present invention provides procedures for identifying agents that can inhibit the cell growth of Staphylococcus aureus, Escherichia coli , or both through the use of rational drug design utilizing the crystallographic data.