The structure of mouse L1210 dihydrofolate reductase‐drug complexes and the construction of a model of human enzyme
- 22 June 1987
- journal article
- research article
- Published by Wiley in FEBS Letters
- Vol. 218 (1), 178-184
- https://doi.org/10.1016/0014-5793(87)81042-6
Abstract
The structure of mouse L1210 dihydrofolate reductase (DHFR) complexed with NADPH and trimethoprim has been refined at 2.0 Å resolution. The analogous complex with NADPH and methotrexate has been refined at 2.5 Å resolution. These structures reveal for the first time details of drug interactions with a mammalian DHFR, which are compared with those observed from previous X‐ray investigations of DHFR/inhibitor complexes. The refined L1210 structure has been used as the basis for the construction of a model of the human enzyme. There are only twenty‐one sequence differences between mouse L1210 and human DHFRs, and all but two of these are located close to the molecular surface: a strong indication that the active sites are essentially identical in these two mammalian enzymes.This publication has 16 references indexed in Scilit:
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