Kinetic investigation of the functional role of phenylalanine-31 of recombinant human dihydrofolate reductase

Biochemistry ◽  
1990 ◽  
Vol 29 (27) ◽  
pp. 6428-6436 ◽  
Author(s):  
Jiu Tsair Tsay ◽  
James R. Appleman ◽  
William A. Beard ◽  
Neal J. Prendergast ◽  
Tavner J. Delcamp ◽  
...  
Keyword(s):  
Dihydrofolate Reductase ◽  
Functional Role ◽  
Kinetic Investigation ◽  
Human Dihydrofolate Reductase

Role of the conserved active site residue tryptophan-24 of human dihydrofolate reductase as revealed by mutagenesis

Biochemistry ◽  
1991 ◽  
Vol 30 (5) ◽  
pp. 1432-1440 ◽  
Author(s):  
William A. Beard ◽  
James R. Appleman ◽  
Shaoming Huang ◽  
Tavner J. Delcamp ◽  
James H. Freisheim ◽  
...  
Keyword(s):  
Dihydrofolate Reductase ◽  
Active Site ◽  
Active Site Residue ◽  
Human Dihydrofolate Reductase

Investigation of the functional role of tryptophan-22 in Escherichia coli dihydrofolate reductase by site-directed mutagenesis

Biochemistry ◽  
1991 ◽  
Vol 30 (46) ◽  
pp. 11092-11103 ◽  
Author(s):  
Mark S. Warren ◽  
Katherine A. Brown ◽  
Martin F. Farnum ◽  
Elizabeth E. Howell ◽  
Joseph Kraut
Keyword(s):  
Escherichia Coli ◽  
Dihydrofolate Reductase ◽  
Functional Role ◽  
Site Directed Mutagenesis ◽  
Directed Mutagenesis

Probing the functional role of phenylalanine-31 of Escherichia coli dihydrofolate reductase by site-directed mutagenesis

Biochemistry ◽  
1987 ◽  
Vol 26 (13) ◽  
pp. 4093-4100 ◽  
Author(s):  
Jin Tann Chen ◽  
Kazunari Taira ◽  
Chen Pei D. Tu ◽  
Stephen J. Benkovic
Keyword(s):  
Escherichia Coli ◽  
Dihydrofolate Reductase ◽  
Functional Role ◽  
Site Directed Mutagenesis ◽  
Directed Mutagenesis

Functional role of aspartic acid-27 in dihydrofolate reductase revealed by mutagenesis

Science ◽  
1986 ◽  
Vol 231 (4742) ◽  
pp. 1123-1128 ◽  
Author(s):  
E. Howell ◽  
J. Villafranca ◽  
M. Warren ◽  
S. Oatley ◽  
J Kraut
Keyword(s):  
Aspartic Acid ◽  
Dihydrofolate Reductase ◽  
Functional Role

Functional role of a mobile loop of Escherichia coli dihydrofolate reductase in transition-state stabilization

Biochemistry ◽  
1992 ◽  
Vol 31 (34) ◽  
pp. 7826-7833 ◽  
Author(s):  
Luyuan Li ◽  
Peter E. Wright ◽  
Stephen J. Benkovic ◽  
Christopher J. Falzone
Keyword(s):  
Escherichia Coli ◽  
Transition State ◽  
Dihydrofolate Reductase ◽  
Functional Role ◽  
Transition State Stabilization

scholarly journals Computer modeling studies of the structural role of NADPH binding to active site mutants of human dihydrofolate reductase in complex with piritrexim.

2001 ◽  
Vol 48 (4) ◽  
pp. 903-916 ◽  
Author(s):  
W Nowak ◽  
V Cody ◽  
A Wojtczak
Keyword(s):  
Dihydrofolate Reductase ◽  
Active Site ◽  
Structural Changes ◽  
Energy Substitution ◽  
Energy Simulations ◽  
Detailed Computer ◽  
Human Dihydrofolate Reductase ◽  
Folate Cycle ◽  
Active Site Mutants

Dihydrofolate reductase (DHFR, EC 1.5.1.3) is one of the enzymes active in the folate cycle which plays an important role in DNA synthesis. Inhibition of DHFR is a key element in the treatment of many diseases, including cancer and AIDS related infections. A search for new selective inhibitors is motivated by the resistance to common drugs observed in the course of treatment. In this paper, results of a detailed computer analysis of human DHFR interactions with the lipophilic inhibitor piritrexim (PTX) are presented. It was found that the NADPH cofactor contributes 30% of the total PTX-enzyme interaction energy. Substitution of the highly conserved Glu30 with alanine does not lead to the release of the inhibitor from the hDHFR pocket. The important L22F point mutation does affect PTX orientation but does not changethe binding energy. Simulations of the dynamics of binary hDHFR-PTX complexes were performed with the use of Extensible Systematic Force Field (ESFF) and the results indicate structural changes in the enzyme induced by NADPH binding.

Critical Role of Phenylalanine 34 of Human Dihydrofolate Reductase in Substrate and Inhibitor Binding and in Catalysis

Biochemistry ◽  
1994 ◽  
Vol 33 (33) ◽  
pp. 9945-9952 ◽  
Author(s):  
Takayuki Nakano ◽  
H. Trent Spencer ◽  
James R. Appleman ◽  
Raymond L. Blakley
Keyword(s):  
Dihydrofolate Reductase ◽  
Critical Role ◽  
Inhibitor Binding ◽  
Human Dihydrofolate Reductase
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