9GVX

M2 mutant (R111K:Y134F:T54V:R132Q:P39Y:R59Y) of human cellular retinoic acid binding protein II - 1e conjugate

これはPDB形式変換不可エントリーです。

9GVX の概要

• エントリーDOI: 10.2210/pdb9gvx/pdb
• 分子名称: Cellular retinoic acid-binding protein 2, methyl (~{Z})-3-(4-ethynylphenyl)-2-methyl-prop-2-enoate (3 entities in total)
• 機能のキーワード: human cellular retinoic acid binding protein ii, hcrabpii, conjugate, chromophore, m2, transport protein
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 16192.50

構造登録者

Tassone, G.,Pozzi, C. (登録日: 2024-09-26, 公開日: 2025-03-26, 最終更新日: 2025-04-02)

主引用文献

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

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: 40104796
DOI: 10.1021/acsmedchemlett.4c00479

実験手法

X-RAY DIFFRACTION (2.1 Å)