Vertex Pharmaceuticals, Inc.

Other

James P Griffith

Keith P Wilson

Eunice E Kim

Joseph L Kim

David M Armistead

David J Livingston

Michael D Sintchak

Mark Andrew Fleming

John Allan Thomson

Matthew James Fitzgibbon

Lovorka Swenson

Kumkum Saxena

Carlos H Faerman

Judith A Lippke

James Roger Black

Michael Andrew Wynn

Fan Lu

The invention relates to FMS-like tyrosine kinase (FLT3), FLT3 binding pockets or FLT3-like binding pockets. The invention relates to a computer comprising a data storage medium encoded with the structure coordinates of such binding pockets. The invention also relates to methods of using the structure coordinates to solve the structure of homologous proteins or protein complexes. The invention relates to methods of using the structure coordinates to screen for and design compounds that bind to FMS-like tyrosine kinase protein, complexes of FMS-like tyrosine kinase protein, homologues thereof, or FLT-3-like protein or protein complexes. The invention also relates to crystallizable compositions and crystals comprising an FMS-like tyrosine kinase cytoplasmic domain or homologues thereof. The invention also relates to methods of identifying inhibitors of the cytoplasmic domain of FMS-like tyrosine kinase protein.

Crystal structure of FMS-like tyrosine kinase

The present invention relates to crystallized molecules and molecular complexes which comprise the active site binding pocket or the FKBP12/FK506 binding pocket of calcineurin or close structural homologues to either binding pocket. This invention also relates to a data storage material encoded with the corresponding structure coordinates of those crystallized molecules or molecular complexes. Such data storage material is capable of displaying such molecules and molecular complexes as a graphical three-dimensional representation on a computer screen. In addition, this invention relates to methods of using the structure coordinates of those molecules or molecular complexes to solve the structure of homologous proteins. This invention also relates to methods of using the structure coordinates to screen and design compounds that bind to calcineurin or homologues thereof.

Molecules comprising a calcineurin-like binding pocket and encoded data storage medium capable of graphically displaying them

Interleukin-1.beta. converting enzyme ('ICE') processes an inactive precursor to the pro-inflammatory cytokine, interleukin-1.beta.. The high-resolution structure of human ICE crystallized in complex with an inhibitor is determined by X-ray diffraction. The active site spans both the 10 and 20 kilodalton subunits. The accessory binding site is composed of residues from the p10 and p20 subunits that are adjacent to the two-fold axis of the crystal. The structure coordinates of the enzyme may be used to design novel classes of ICE inhibitors.

Crystal structure and mutants of interleukin-1.beta. converting enzyme

Molecules comprising a calcineurin-like binding pocket and encoded data

Crystal structure and mutants of interleukin-1 beta converting enzyme

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Weston, MA, United States of America

James P Griffith