2lf1

Solution structure of L. casei dihydrofolate reductase complexed with NADPH, 30 structures

spinqualitylabelsall models 2lf1, 30 NMR models Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2lf1 is a 1 chain structure with sequence from "bacillus_a"_von_freudenreich_1890 "bacillus a" von freudenreich 1890. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: NDP Related: 2l28, 1lud, 2hm9 Gene: folA, dhfR ("Bacillus a" von Freudenreich 1890) Activity: Dihydrofolate reductase, with EC number 1.5.1.3 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [DYR_LACCA] Key enzyme in folate metabolism. Catalyzes an essential reaction for de novo glycine and purine synthesis, and for DNA precursor synthesis. Publication Abstract from PubMed In order to examine the origins of the large positive cooperativity (Gcoop = -2.9 kcal mol-1) of trimethoprim (TMP) binding to a bacterial dihydrofolate reductase (DHFR) in the presence of NADPH we have determined and compared NMR solution structures of L. casei apo DHFR and its binary and ternary complexes with TMP and NADPH, and made complementary thermodynamic measurements. The DHFR structures are generally very similar except for the A-B loop region and part of helix B (residues 15-31) which could not be directly detected for L. casei apo DHFR because of line-broadening from exchange between folded and unfolded forms. Thermodynamic and NMR measurements suggested that a significant but not dominant contribution to the cooperativity comes from refolding of apo DHFR on binding the first ligand (up to -0.7 kcals mol-1 estimated for A-B loop refolding). Comparisons of C-C distance differences and domain rotation angles between apo DHFR and its complexes indicated that generally similar conformational changes involving domain movements accompany formation of the binary complexes with either TMP or NADPH, and that the binary structures are approaching that of the ternary complex as would be expected for positive cooperativity. These favorable ligand-induced structural changes upon binding the first ligand will also contribute significantly to the cooperative binding. A further substantial contribution to cooperative binding results from the proximity of the bound ligands in the ternary complex: this reduces the solvent accessible area of the ligand and provides a favorable entropic hydrophobic contribution (up to -1.4 kcal mol-1). NMR structures of apo L.casei dihydrofolate reductase and its complexes with trimethoprim and NADPH. Contributions to positive cooperative binding from ligand-induced refolding, conformational changes and interligand hydrophobic interactionsdagger.,Feeney J, Birdsall B, Kovalevskaya NV, Smurnyy YD, Navarro-Peran EM, Polshakov VI Biochemistry. 2011 Mar 16. PMID:21410224 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Dihydrofolate reductase

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