The crystal structure of \(E\). coli dihydrofolate reductase (DFR) with NADP \(^{+}\) and folate bound can be found in the Protein Data Bank (www.rcsb.org/pdb) as file 7 DFR. Go to this website, enter "7DFR" in the search line, and click on "KiNG" under "Display options" when the 7 DFR page comes up. Explore the KiNG graphic of the DFR structure to visualize how its substrates are bound. (If you hold down the left button on your mouse and move the cursor over the image, you can rotate the structure to view it from different perspectives.) Note in particular the spatial relationship between the nicotinamide ring of \(\mathrm{NADP}^{+}\) and the pterin ring of folate. Do you now have a better appreciation for how this enzyme works? Note also the location of polar groups on the two substrates in relation to the DFR structure.

The Protein Data Bank (PDB) is an invaluable resource for students and researchers interested in molecular biology. It serves as a library for the three-dimensional structural data of large biological molecules, such as proteins and nucleic acids. Imagine it as an expansive catalog where detailed protein structures are archived. These structures are obtained through experimental methods like X-ray crystallography, NMR spectroscopy, and cryo-electron microscopy.

For students exploring biochemistry, the PDB acts as a virtual window allowing them to peek into the molecular world, facilitating a deeper understanding of how proteins function at an atomic level. The availability of such detailed structural information aids in the study of biological processes and in the development of pharmaceuticals. Specifically, using the PDB code '7DFR', one can visualize the intricate details of the dihydrofolate reductase structure, which is fundamental in understanding its role in the cell.

Enzyme-substrate interaction is a cornerstone concept in biochemistry, illustrating how an enzyme binds to its substrate to catalyze a chemical reaction. This interaction is not only about the physical binding but also about how the enzyme's shape complements its substrate, often analogized to a key fitting in a lock—popularly known as the 'lock-and-key' model.

For the enzyme dihydrofolate reductase (DFR), understanding this interaction can provide insights into its mechanism of action. This enzyme plays a critical role in the synthesis of DNA, RNA, and proteins by reducing dihydrofolate to tetrahydrofolate using NADPH as an electron donor. By visualizing the enzyme-substrate complex, students can appreciate how the precise positioning of substrate molecules is essential for efficient catalysis, therefore grasping the importance of shape and charge in these biological processes.

Dihydrofolate reductase (DFR) binds two essential substrates: NADP+ and folate. The binding sites for these substrates are designed to perfectly fit their molecular structures, which is fundamental to the enzyme's function. NADP+ acts as an electron donor in the reaction, and folate is the substrate being reduced.

By examining the crystal structure of DFR with bound NADP+ and folate, we learn about the specific interactions that stabilize these substrates within the enzyme's active site. Notably, the spatial proximity between the nicotinamide ring of NADP+ and the pterin ring of folate is crucial for the transfer of electrons necessary for the reduction process. Moreover, the presence and position of polar groups are also critical since they contribute to the proper orientation and binding stability of these molecules, influencing the enzyme's catalytic efficiency.

3D protein visualization tools, like KiNG, provide an interactive way to explore the structure of proteins in three dimensions. This aids in visualizing how proteins, like dihydrofolate reductase, function within a cell. Through the use of these tools, students can rotate and zoom in on the protein structure to observe the positioning of substrates and identify active sites and important interactions within the enzyme.

Observing a protein in 3D can significantly enhance a student's understanding of molecular biology. By manipulating the structure, one can see how different parts of the enzyme are related spatially, which is often challenging to grasp from static 2D images. Learning to use these visualization tools not only benefits one's immediate understanding of a structure but also develops skills relevant to fields like drug design and protein engineering where spatial understanding is vital.