5ssu

DHFR:NADP+:FOL complex at 270 K (crystal 3)

spinqualitylabelsall models 5ssu, resolution 1.12Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5ssu is a 1 chain structure with sequence from Escherichia coli K-12. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.12Å Ligands: CSD, FOL, MN, NAP Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function DYR_ECOLI 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 Enzymes catalyze biochemical reactions through precise positioning of substrates, cofactors, and amino acids to modulate the transition-state free energy. However, the role of conformational dynamics remains poorly understood due to poor experimental access. This shortcoming is evident with Escherichia coli dihydrofolate reductase (DHFR), a model system for the role of protein dynamics in catalysis, for which it is unknown how the enzyme regulates the different active site environments required to facilitate proton and hydride transfer. Here, we describe ligand-, temperature-, and electric-field-based perturbations during X-ray diffraction experiments to map the conformational dynamics of the Michaelis complex of DHFR. We resolve coupled global and local motions and find that these motions are engaged by the protonated substrate to promote efficient catalysis. This result suggests a fundamental design principle for multistep enzymes in which pre-existing dynamics enable intermediates to drive rapid electrostatic reorganization to facilitate subsequent chemical steps. Perturbative diffraction methods resolve a conformational switch that facilitates a two-step enzymatic mechanism.,Greisman JB, Dalton KM, Brookner DE, Klureza MA, Sheehan CJ, Kim IS, Henning RW, Russi S, Hekstra DR Proc Natl Acad Sci U S A. 2024 Feb 27;121(9):e2313192121. doi: , 10.1073/pnas.2313192121. Epub 2024 Feb 22. PMID:38386706 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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