Takeda San Diego, Inc.

Sloan-kettering Institute for Cancer Research

Nikola P Pavletich

Jacek Nowakowski

Devon A Thompson

Mark Knuth

Ciaran N Cronin

Robert A Wijnands

Victoria M Richon

Ronald C Breslow

Paul A Marks

Richard A Rifkind

Duncan E McRee

Oleg Brodsky

Eric Adam

Michael Finnin

Jill Donigian

Joan Massagu&eacute;

Yigong Shi

Provided are crystals relating to Aurora/LPL1P-related kinase and its various uses.

Crystallization of aurora/LPL1P-related kinase

Provided are crystals relating to human Ephrin Receptor A2 and its various uses.

Wild-type kinase domain of human Ephrin receptor A2 (EPHA2) and crystallization thereof

Provided are crystals relating to AKT3 and its various uses.

Crystallization of AKT3

The present invention provides three-dimensional structural information from the hyperthermophilic bacteriumwhich is a histone deacetylase-like protein (HDLP). HDLP shares 35.2% amino acid sequence identity with human histone deacetylase (HDAC1). The present invention further provides three-dimensional structural information of HDLP bound by inhibitor molecules. The three-dimensional structural information of the present invention is useful to design, isolate and screen deacetylase inhibitor compounds capable of inhibiting HDLP, HDAC family members and HDLP-related molecules. The invention also relates to nucleic acids encoding a mutant HDLP which facilitates the determination of the three-dimensional structure of HDLP in the presence of a zinc atom.

Crystal structure of a deacetylase and inhibitors thereof

Signal transduction by the TGF-&bgr; family involves sets of receptor serine/threonine kinases, Smad proteins that act as receptor substrates, and Smad-associated transcription factors that target specific genes. Discrete structural elements were identified that dictate the selective interactions between receptors and Smads and between Smads and transcription factors in the TGF-&bgr; and BMP pathways. A cluster of four residues in the L45 loop of the type I receptor kinase domain, and a matching set of two residues in the L3 loop of the Smad C-terminal domain establish the specificity of receptor-Smad interactions. A cluster of residues in the highly exposed &agr;-helix 2 of the Smad C-terminal domain specify the interaction with the DNA-binding factor Fast1 and, as a result, the gene responses mediated by the pathway. By establishing specific interactions, these determinants keep the TGF-&bgr; and BMP pathways segregated from each other.

Methods of inhibiting or enhancing the TGF&bgr;-SMAD signaling pathway

Growing community of inventors

New York, NY, United States of America

Nikola P Pavletich