9KZ4
Dihydrofolate reductase binding to NADPH and trimethoprim-tetramethylrhodamine
This is a non-PDB format compatible entry.
Summary for 9KZ4
| Entry DOI | 10.2210/pdb9kz4/pdb |
| Descriptor | Dihydrofolate reductase, NADPH DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE, [9-[5-[2-[4-[[2,4-bis(azanyl)pyrimidin-5-yl]methyl]-2,6-dimethoxy-phenoxy]ethylcarbamoyl]-2-carboxy-phenyl]-6-(dimethylamino)xanthen-3-ylidene]-dimethyl-azanium, ... (5 entities in total) |
| Functional Keywords | enzyme, self-labeling tag, tmp-tag, fluorescence imaging, biosynthetic protein |
| Biological source | Escherichia coli K-12 |
| Total number of polymer chains | 2 |
| Total formula weight | 39099.07 |
| Authors | Zhang, K.C.,Chen, Z.X. (deposition date: 2024-12-09, release date: 2025-01-22, Last modification date: 2026-08-19) |
| Primary citation | Zhang, K.,Zhang, J.,Chen, N.,Chen, Z. Dynamic conformations of fluorophores on self-labeling protein tags. Biophys.J., 125:3978-3994, 2026 Cited by PubMed Abstract: Self-labeling protein tags (SLPs) enable protein-specific conjugation of synthetic fluorophores for versatile bioimaging, yet their rational engineering has largely relied on static structural models. Here, we reveal that crystal structures of SLP-dye complexes generally bear packing artifacts due to strong π-π interactions of dyes, frequently failing to profile the chromophore microenvironment. By integrating molecular dynamics (MD) with crystallography, we elucidate distinct dynamic behaviors of fluorophores across major SLPs: quasi-free diffusion in SNAP-tag, balanced hydrophobic-polar interactions in TMP-tag, and discrete, state-selective anchoring in HaloTag and Rho-tag. Comparisons with the newly developed SNAP-tag2 demonstrate that functional evolution reshapes conformational landscapes rather than merely strengthening binding. We further validate simulation-derived predictions through MD-guided lattice selection. Together, this work establishes a comparative, dynamic framework for understanding SLP-dye interactions beyond crystallography, while providing a conceptual basis for further engineering chemigenetic tools for advanced imaging and sensing. PubMed: 42363595DOI: 10.1016/j.bpj.2026.06.033 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.708 Å) |
Structure validation
Download full validation report
