Probing the Role of an Active Site Aspartic Acid in Dihydrofolate Reductase

1997 ◽  
Vol 119 (35) ◽  
pp. 8166-8176 ◽  
Author(s):  
Vladimir A. Karginov ◽  
Sergey V. Mamaev ◽  
Haoyun An ◽  
Mark D. Van Cleve ◽  
Sidney M. Hecht ◽  
...  
Keyword(s):  
Aspartic Acid ◽  
Dihydrofolate Reductase ◽  
Active Site

Role of Four Conserved Active-Site Aspartic Acid Residues inThermobifida fuscaEndoglucanase Cel6A

2000 ◽  
pp. 28-38
Author(s):  
David B. Wilson ◽  
David Wolfgang ◽  
Sheng Zhang ◽  
Diana Irwin
Keyword(s):  
Aspartic Acid ◽  
Active Site

Role of the Active-Site Carboxylate in Dihydrofolate Reductase: Kinetic and Spectroscopic Studies of the Aspartate 26 .fwdarw. Asparagine Mutant of the Lactobacillus casei Enzyme

Biochemistry ◽  
1995 ◽  
Vol 34 (9) ◽  
pp. 2872-2882 ◽  
Author(s):  
J. Basran ◽  
M. G. Casarotto ◽  
I. L. Barsukov ◽  
G. C. K. Roberts
Keyword(s):  
Dihydrofolate Reductase ◽  
Active Site ◽  
Lactobacillus Casei ◽  
Spectroscopic Studies

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

The catalytic role of the active site aspartic acid in serine proteases

Science ◽  
1987 ◽  
Vol 237 (4817) ◽  
pp. 909-913 ◽  
Author(s):  
C. Craik ◽  
S Roczniak ◽  
C Largman ◽  
W. Rutter
Keyword(s):  
Aspartic Acid ◽  
Active Site ◽  
Serine Proteases ◽  
Catalytic Role

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

Role of Active Site Loop Dynamics in Mediating Ligand Release from E. coli Dihydrofolate Reductase

Biochemistry ◽  
2021 ◽  
Author(s):  
Amrinder Singh ◽  
R. Bryn Fenwick ◽  
H. Jane Dyson ◽  
Peter E. Wright
Keyword(s):  
Dihydrofolate Reductase ◽  
Active Site ◽  
E Coli ◽  
Loop Dynamics

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.

scholarly journals Defining the role of active-site loop fluctuations in dihydrofolate reductase catalysis

2005 ◽  
Vol 102 (14) ◽  
pp. 5032-5037 ◽  
Author(s):  
D. McElheny ◽  
J. R. Schnell ◽  
J. C. Lansing ◽  
H. J. Dyson ◽  
P. E. Wright
Keyword(s):  
Dihydrofolate Reductase ◽  
Active Site

Structural and Biochemical Characterization of a Copper-Binding Mutant of the Organomercurial Lyase MerB: Insight into the Key Role of the Active Site Aspartic Acid in Hg–Carbon Bond Cleavage and Metal Binding Specificity

Biochemistry ◽  
2016 ◽  
Vol 55 (7) ◽  
pp. 1070-1081 ◽  
Author(s):  
Haytham M. Wahba ◽  
Lauriane Lecoq ◽  
Michael Stevenson ◽  
Ahmed Mansour ◽  
Laurent Cappadocia ◽  
...  
Keyword(s):  
Aspartic Acid ◽  
Active Site ◽  
Metal Binding ◽  
Biochemical Characterization ◽  
Bond Cleavage ◽  
Copper Binding ◽  
Organomercurial Lyase ◽  
Insight Into
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