Insights into Enzymic Catalysis from Studies on Dihydrofolate Reductases
The role of DHFR in the maintenance of cellular DNA has sparked wide interest in the structure and dynamics of this enzyme. Kinetic studies of specific amino acid replacements on the enzyme isolated from E. coli has proved useful in the detailing of hydrophobic and ionic interactions both proximal a...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
| Published: |
De Gruyter
1989-02-01
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| Series: | Pteridines |
| Online Access: | https://doi.org/10.1515/pteridines.1989.1.1.37 |
| _version_ | 1831568093795581952 |
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| author | Benkovic Stephen J. Adams Joseph A. Fierke Carol A. Naylor Adel M. |
| author_facet | Benkovic Stephen J. Adams Joseph A. Fierke Carol A. Naylor Adel M. |
| author_sort | Benkovic Stephen J. |
| collection | DOAJ |
| description | The role of DHFR in the maintenance of cellular DNA has sparked wide interest in the structure and dynamics of this enzyme. Kinetic studies of specific amino acid replacements on the enzyme isolated from E. coli has proved useful in the detailing of hydrophobic and ionic interactions both proximal and distal to the site of chemical transformation (e. g. Phe-31, Leu-54 and Arg-44). Despite the low sequence homology shared by the E. coli and L. easei enzymes, the free energy profiles are surprisingly comparable. This probably is the result of the high degree of structural similarity of the active site surfaces, but the deleterious effects of subtle replacements (e. g. Leu-54-Ile) at strictly conserved amino acids underscore the latters unique role in attaining the required catalytic efficiency for the enzyme. |
| first_indexed | 2024-12-17T12:09:54Z |
| format | Article |
| id | doaj.art-f2278924750741f483003b10424ece5d |
| institution | Directory Open Access Journal |
| issn | 0933-4807 2195-4720 |
| language | English |
| last_indexed | 2024-12-17T12:09:54Z |
| publishDate | 1989-02-01 |
| publisher | De Gruyter |
| record_format | Article |
| series | Pteridines |
| spelling | doaj.art-f2278924750741f483003b10424ece5d2022-12-21T21:49:28ZengDe GruyterPteridines0933-48072195-47201989-02-0111374310.1515/pteridines.1989.1.1.37Insights into Enzymic Catalysis from Studies on Dihydrofolate ReductasesBenkovic Stephen J.0Adams Joseph A.1Fierke Carol A.2Naylor Adel M.3Department of Chemistry, The Pennsylvania State University, University Park, PA 16802, U.S.A.Department of Chemistry, The Pennsylvania State University, University Park, PA 16802, U.S.A.Duke University Medical Center, Biochemistry Department, Box 3711 , Durham, N.C. 27710, U.S.A.California Institute of Technology, Department of Chemistry, California Institute of Technology, Pasadena, CA 91125, U.S.A.The role of DHFR in the maintenance of cellular DNA has sparked wide interest in the structure and dynamics of this enzyme. Kinetic studies of specific amino acid replacements on the enzyme isolated from E. coli has proved useful in the detailing of hydrophobic and ionic interactions both proximal and distal to the site of chemical transformation (e. g. Phe-31, Leu-54 and Arg-44). Despite the low sequence homology shared by the E. coli and L. easei enzymes, the free energy profiles are surprisingly comparable. This probably is the result of the high degree of structural similarity of the active site surfaces, but the deleterious effects of subtle replacements (e. g. Leu-54-Ile) at strictly conserved amino acids underscore the latters unique role in attaining the required catalytic efficiency for the enzyme.https://doi.org/10.1515/pteridines.1989.1.1.37 |
| spellingShingle | Benkovic Stephen J. Adams Joseph A. Fierke Carol A. Naylor Adel M. Insights into Enzymic Catalysis from Studies on Dihydrofolate Reductases Pteridines |
| title | Insights into Enzymic Catalysis from Studies on Dihydrofolate Reductases |
| title_full | Insights into Enzymic Catalysis from Studies on Dihydrofolate Reductases |
| title_fullStr | Insights into Enzymic Catalysis from Studies on Dihydrofolate Reductases |
| title_full_unstemmed | Insights into Enzymic Catalysis from Studies on Dihydrofolate Reductases |
| title_short | Insights into Enzymic Catalysis from Studies on Dihydrofolate Reductases |
| title_sort | insights into enzymic catalysis from studies on dihydrofolate reductases |
| url | https://doi.org/10.1515/pteridines.1989.1.1.37 |
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