Structures of apo and complexed Escherichia coli glycinamide ribonucleotide transformylase.
The three-dimensional structure of phosphoribosylglycinamide formyltransferase (10-formyltetrahydrofolate:5'-phosphoribosylglycinamide formyltransferase, EC 2.1.2.2) has been solved both as an apoenzyme at 2.8-A resolution and as a ternary complex with the substrate glycinamide ribonucleotide and a folate inhibitor at 2.5-A resolution. The structure is a modified doubly wound alpha/beta sheet with flexibility in the active site, including a disordered loop in the apo structure, which is ordered in the ternary complex structure. This enzyme is a target for anti-cancer therapy and now for structure-based drug design.
Almassy
R J
RJ
Agouron Pharmaceuticals, San Diego, CA 92121.
Janson
C A
CA
Kan
C C
CC
Hostomska
Z
Z
D000217:Acyltransferases / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000648:ultrastructure*; D001059:Apoproteins / Q000648:ultrastructure; D001665:Binding Sites; D003196:Computer Graphics; D003461:Crystallography; D004926:Escherichia coli / Q000201:enzymology*; D006860:Hydrogen Bonding; D019877:Hydroxymethyl and Formyl Transferases; D008958:Models, Molecular; D051026:Phosphoribosylglycinamide Formyltransferase; D011487:Protein Conformation; D011994:Recombinant Proteins; D014961:X-Ray Diffraction
D001059:Apoproteins; D011994:Recombinant Proteins; D019877:Hydroxymethyl and Formyl Transferases; D051026:Phosphoribosylglycinamide Formyltransferase; D000217:Acyltransferases