Three-dimensional structure of prostaglandin d synthase and utilization thereof

Abstract

A method of designing an anti-allergic agent, sleep controlling agent, anti-obesity agent and remedy for brain injury acting via the inhibition of biosynthesis of prostaglandin D 2 . Crystal of a complex of human origin hematopoietic prostaglandin D synthase, glutathione, and a substrate analog or an inhibitor, etc are prepared and the three-dimensional structural coordinate of each atom in the complex is determined by X-ray crystal analysis.

1 - 17 . (canceled) 
     
     
         18 . A method for selecting an inhibitor of human hematopoietic PGDS, comprising steps of:
 (a) providing at least one structural coordinate selected from the group consisting of structural coordinates represented in Table 1-8 which characterizes an active site of human hematopoietic PGDS;   (b) providing steric structure of a candidate compound; and   (c) fitting the candidate to the active site of human hematopoietic PGDS to select the inhibitor.   
     
     
         19 . A method in accordance with  claim 18  which further comprising:
 (d) contacting the selected compound with the enzyme in the presence of prostaglandin H 2  to confirm an ability of the compound to inhibit the enzymatic activity of PGDS.   
     
     
         20 . A method in accordance with  claim 18  which further comprising measuring whether the inhibitor has at least one biological activity selected the group consisting of anti-allergic activity, sleep control activity, anti-obesity activity and brain wound healing activity. 
     
     
         21 - 22 . (canceled) 
     
     
         23 . A method in accordance with  claim 19  which further comprising measuring whether the inhibitor has at least one biological activity selected the group consisting of anti-allergic activity, sleep control activity, anti-obesity activity and brain wound healing activity.