The Z isomer of 2,4-diaminofuro[2,3-d]pyrimidine antifolate promotes unusual crystal packing in a human dihydrofolate reductase ternary complex
August 19th, 2009 Posted by: admin
The crystal structure of the ternary complex of human dihydrofolate reductase (hDHFR) with NADPH and the Z isomer of 2,4-diamino-5-[2-(2'-methoxyphenyl)propenyl]-furo[2,3-d]pyrimidine (Z1) shows that the Z isomer binds in the normal antifolate orientation in which the furo oxygen occupies the 8-amino position observed in the binding of 2,4-diaminopteridine antifolates such as methotrexate and with the methoxyphenyl moiety cis to and coplanar with the furo[2,3-d]pyrimidine ring. The hDHFR ternary complex crystallized in the orthorhombic space group P212121 and its structure was refined to 1.7 Ã resolution. Although other hDHFR complexes crystallize in this space group, these data provide only the second example of an unusual packing arrangement in which the conserved
