9GVY
M2 mutant (R111K:Y134F:T54V:R132Q:P39Y:R59Y) of human cellular retinoic acid binding protein II - 1m conjugate
This is a non-PDB format compatible entry.
Summary for 9GVY
| Entry DOI | 10.2210/pdb9gvy/pdb |
| Descriptor | Cellular retinoic acid-binding protein 2, methyl (~{Z})-2-methyl-3-(4-nitrophenyl)prop-2-enoate (3 entities in total) |
| Functional Keywords | human cellular retinoic acid binding protein ii, hcrabpii, conjugate, chromophore, m2, transport protein |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 1 |
| Total formula weight | 16213.47 |
| Authors | Tassone, G.,Pozzi, C. (deposition date: 2024-09-26, release date: 2025-03-26, Last modification date: 2025-04-02) |
| Primary citation | Paolino, M.,Tassone, G.,Governa, P.,Saletti, M.,Lami, M.,Carletti, R.,Sacchetta, F.,Pozzi, C.,Orlandini, M.,Manetti, F.,Olivucci, M.,Cappelli, A. Morita-Baylis-Hillman Adduct Chemistry as a Tool for the Design of Lysine-Targeted Covalent Ligands. Acs Med.Chem.Lett., 16:397-405, 2025 Cited by PubMed Abstract: The use of Targeted Covalent Inhibitors (TCIs) is an expanding strategy for the development of innovative drugs. It is driven by two fundamental steps: (1) recognition of the target site by the molecule and (2) establishment of the covalent interaction by its reactive group. The development of new TCIs depends on the development of new warheads. Here, we propose the use of Morita-Baylis-Hillman adducts (MBHAs) to covalently bind Lys strategically placed inside a lipophilic pocket. A human cellular retinoic acid binding protein II mutant (M2) was selected as a test bench for a library of 19 MBHAs. The noncovalent interaction step was investigated by molecular docking studies, while experimentally the entire library was incubated with M2 and crystallized to confirm covalent binding with the target lysine. The results, rationalized through covalent docking analysis, support our hypothesis of MBHAs as reactive scaffolds for the design of lysine-TCIs. PubMed: 40104796DOI: 10.1021/acsmedchemlett.4c00479 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.05 Å) |
Structure validation
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