Yale University

Rib-x Pharmaceuticals, Inc.

Melinta Therapeutics, Inc.

Jeffrey L Hansen

Thomas A Steitz

Peter B Moore

Nenad Ban

Poul Nissen

Joseph A Ippolito

The present invention provides methods for producing high resolution crystals of ribosomes and ribosomal subunits as well as the crystals produced by such methods. The x-ray diffraction patterns of the crystals provided by the present invention are of sufficiently high resolution for determining the three-dimensional structure of ribosomes and ribosomal subunits, for identifying ligand binding sites on ribosomes and ribosomal subunits, and for molecular modeling of ligands which interact with ribosomes and ribosomal subunits. The present invention provides methods for identifying ribosome-related ligands and methods for designing ligands with specific ribosome-binding properties. Thus, the methods of the present invention may be used to produce ligands which are designed to kill or inhibit any specific target organism(s).

Determination and uses of the atomic structures of ribosomes and ribosomal subunits and their ligand complexes

The invention provides methods for producing high resolution crystals of ribosomes and ribosomal subunits as well as crystals produced by such methods. The invention also provides high resolution structures of ribosomal subunits either alone or in combination with protein synthesis inhibitors. The invention provides methods for identifying ribosome-related ligands and methods for designing ligands with specific ribosome-binding properties as well as ligands that may act as protein synthesis inhibitors. Thus, the methods and compositions of the invention may be used to produce ligands that are designed to specifically kill or inhibit the growth of any target organism.

Modulators of ribosomal function and identification thereof

Method of identifying molecules that bind to the large ribosomal subunit

Crystals of the large ribosomal subunit

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Charleston, SC, United States of America

Jeffrey L Hansen