scholarly journals Role of Y94 in Proton and Hydride Transfers Catalyzed by Thymidylate Synthase†

Biochemistry ◽  
2007 ◽  
Vol 46 (49) ◽  
pp. 14188-14197 ◽  
Author(s):  
Baoyu Hong ◽  
Frank Maley ◽  
Amnon Kohen
Keyword(s):  
1989 ◽  
Vol 264 (32) ◽  
pp. 19132-19137
Author(s):  
I K Dev ◽  
B B Yates ◽  
J Atashi ◽  
W S Dallas

2008 ◽  
Vol 6 (12) ◽  
pp. 150
Author(s):  
P. Phatak ◽  
C.M. Daniels ◽  
A.F. Shields ◽  
J.M. Collins ◽  
P.M. LoRusso ◽  
...  

1999 ◽  
Vol 56 (5) ◽  
pp. 1063-1070 ◽  
Author(s):  
Maria E. Kitchens ◽  
Antonia M. Forsthoefel ◽  
Karen W. Barbour ◽  
H. Trent Spencer ◽  
Franklin G. Berger

Author(s):  
H. H. J. Backus ◽  
H. M. Pinedo ◽  
D. Wouters ◽  
M. C. Koudijs ◽  
C. G. Ferreira ◽  
...  

1987 ◽  
Vol 149 (3) ◽  
pp. 1200-1207 ◽  
Author(s):  
Jolanta M. Dzik ◽  
Tadeusz Kulikowski ◽  
Zbigniew Zielinski ◽  
Joanna Ciesla ◽  
Wojciech Rode ◽  
...  
Keyword(s):  

2013 ◽  
Author(s):  
Lidia V. Kulemina ◽  
Min Chen ◽  
Kyungah Maeng ◽  
Akbar Nawab ◽  
Maria Zajac-Kaye

Blood ◽  
1998 ◽  
Vol 91 (11) ◽  
pp. 4350-4360 ◽  
Author(s):  
Ronald M. Laethem ◽  
Yusuf A. Hannun ◽  
Supriya Jayadev ◽  
Connie J. Sexton ◽  
Jay C. Strum ◽  
...  

Abstract Thymidylate synthase (TS) inhibition causes cell death, and this enzyme is the target for the important chemotherapy regime 5-fluorouracil/leucovorin. GW1843 (1843U89) is a potent and specific folate analog TS inhibitor in clinical development. Because of the importance of TS as a chemotherapy target, we are studying the mechanism of TS inhibition-induced cell death by GW1843. Ceramide is a regulatory lipid generated by the action of sphingomyelinase and is believed to signal apoptosis. The role of the ceramide in apoptotic signaling was studied in Molt-4 human T-cell leukemia cells undergoing cell death after treatment with GW1843. In response to GW1843, Molt-4 cells undergo apoptosis with both acidic pH, Mg2+-independent sphingomyelinase (ASMase) and neutral pH, Mg2+-dependent sphingomyelinase (NSMase) activities elevated as early steps in the initiation of apoptosis before Molt-4 commitment to death. These activities lead to ceramide production with kinetics consistent with a role as an effector molecule signaling the initiation of apoptosis in Molt-4 cells. These changes were found to be independent of caspase 3–like (CPP32/apopain) activity and DNA degradation, but were not separable from membrane blebbing or cell lysis in this cell line. In this report, kinetic evidence is provided for a role of ceramide in initiating GW1843-induced cell death of Molt-4 T-cell leukemia cells.


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