Patent ID: 6312887
Filing Date: 2001-11-06
Classification: C07K

Abstract:
A method of identifying a compound that binds to the N-terminal domain of a Signal Transducer And Activator of Transcription (STAT) comprising:(a) obtaining a set of atomic coordinates defining the three-dimensional structure of a crystal of an N-terminal fragment of a STAT that effectively diffracts X-rays for the determination of the atomic coordinates of the N-terminal fragment to a resolution of better than 5.0 Angstroms; wherein the N-terminal fragment of the STAT protein consists of 122 to 128 amino acid residues and comprises a peptide consisting of amino acid residues 2-123 of SEQ ID NO:9; and wherein said crystal has a space group of P6.sub.5 22 with unit cell dimensions of a=79.51 .ANG., b=79.51 .ANG., and c=84.68 .ANG.;(b) selecting a compound by performing rational drug design with the atomic coordinates obtained in step (a), wherein said selecting is performed in conjunction with computer modeling;(c) contacting the compound with a dimeric STAT protein N-terninal domain; and(d) detecting the binding of the compound with the N-terminal domain; wherein a compound is selected that binds to the N-terminal domain.