7DFR
CRYSTAL STRUCTURES OF ESCHERICHIA COLI DIHYDROFOLATE REDUCTASE. THE NADP+ HOLOENZYME AND THE FOLATE(DOT)NADP+ TERNARY COMPLEX. SUBSTRATE BINDING AND A MODEL FOR THE TRANSITION STATE
Summary for 7DFR
Entry DOI | 10.2210/pdb7dfr/pdb |
Descriptor | DIHYDROFOLATE REDUCTASE, FOLIC ACID, NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE, ... (4 entities in total) |
Functional Keywords | oxido-reductase, oxidoreductase |
Biological source | Escherichia coli |
Total number of polymer chains | 1 |
Total formula weight | 19205.13 |
Authors | Bystroff, C.,Oatley, S.J.,Kraut, J. (deposition date: 1988-10-21, release date: 1990-07-15, Last modification date: 2024-10-30) |
Primary citation | Bystroff, C.,Oatley, S.J.,Kraut, J. Crystal structures of Escherichia coli dihydrofolate reductase: the NADP+ holoenzyme and the folate.NADP+ ternary complex. Substrate binding and a model for the transition state. Biochemistry, 29:3263-3277, 1990 Cited by PubMed Abstract: The crystal structure of dihydrofolate reductase (EC 1.5.1.3) from Escherichia coli has been solved as the binary complex with NADP+ (the holoenzyme) and as the ternary complex with NADP+ and folate. The Bragg law resolutions of the structures are 2.4 and 2.5 A, respectively. The new crystal forms are nonisomorphous with each other and with the methotrexate binary complex reported earlier [Bolin, J. T., Filman, D. J., Matthews, D. A., Hamlin, R. C., & Kraut, J. (1982) J. Biol. Chem. 257, 13650-13662]. In general, NADP+ and folate binding conform to predictions, but the nicotinamide moiety of NADP+ is disordered in the holoenzyme and ordered in the ternary complex. A mobile loop (residues 16-20) involved in binding the nicotinamide is also disordered in the holoenzyme. We report a detailed analysis of the binding interactions for both ligands, paying special attention to several apparently strained interactions that may favor the transition state for hydride transfer. Hypothetical models are presented for the binding of 7,8-dihydrofolate in the Michaelis complex and for the transition-state complex. PubMed: 2185835DOI: 10.1021/bi00465a018 PDB entries with the same primary citation |
Experimental method | X-RAY DIFFRACTION (2.5 Å) |
Structure validation
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