TY - JOUR
T1 - Divergent regulation of dihydrofolate reductase between malaria parasite and human host
AU - Zhang, Kai
AU - Rathod, Pradipsinh K.
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2002/4/19
Y1 - 2002/4/19
N2 - For half a century, successful antifolate therapy against Plasmodium falciparum malaria has been attributed to host-parasite differences in drug binding to dihydrofolate reductase-thymidylate synthase (DHFR-TS). Selectivity may also arise through previously unappreciated differences in regulation of this drug target. The DHFR-TS of Plasmodium binds its cognate messenger RNA (mRNA) and inhibits its own translation. However, unlike translational regulation of DHFR or TS in humans, DHFR-TS mRNA binding is not coupled to enzyme active sites. Thus, antifolate treatment does not relieve translational inhibition and parasites cannot replenish dead enzyme.
AB - For half a century, successful antifolate therapy against Plasmodium falciparum malaria has been attributed to host-parasite differences in drug binding to dihydrofolate reductase-thymidylate synthase (DHFR-TS). Selectivity may also arise through previously unappreciated differences in regulation of this drug target. The DHFR-TS of Plasmodium binds its cognate messenger RNA (mRNA) and inhibits its own translation. However, unlike translational regulation of DHFR or TS in humans, DHFR-TS mRNA binding is not coupled to enzyme active sites. Thus, antifolate treatment does not relieve translational inhibition and parasites cannot replenish dead enzyme.
UR - http://www.scopus.com/inward/record.url?scp=0037134042&partnerID=8YFLogxK
U2 - 10.1126/science.1068274
DO - 10.1126/science.1068274
M3 - Article
C2 - 11964483
AN - SCOPUS:0037134042
VL - 296
SP - 545
EP - 547
JO - Science
JF - Science
SN - 0036-8075
IS - 5567
ER -