Patent ID: 6225076
Filing Date: 2001-05-01
Classification: C07K,C12N,C12Q,G01N,G16B

Abstract:
A method of identifying an agent for use as an inhibitor of bacterial RNA polymerase comprising:(a) obtaining a set of atomic coordinates defining the three-dimensional structure of the core RNA polymerase (RNAP) from T. aquaticus consisting essentially of the .beta.', .beta., .alpha. and .omega. subunits of RNAP from T. aquaticus and using a crystal having the space group of P4.sub.1 2.sub.1 2 and unit cell dimensions of a=b=201 and c=294 .ANG.;(b) selecting a potential agent 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 potential agent with a bacterial RNA polymerase; and(d) measuring the activity of the bacterial RNA polymerase; wherein a potential agent is identified as an agent that inhibits bacterial RNA polymerase when there is a decrease in the activity of the bacterial RNA polymerase in the presence of the agent relative to in its absence.