32SN

CRYSTAL STRUCTURE OF BRD4-BD1 IN COMPLEX WITH COMPOUND 13

32SN の概要

• エントリーDOI: 10.2210/pdb32sn/pdb
• 関連するPDBエントリー: 32PP 32RX 32RY 32RZ 32SB 32SC
• 分子名称: Bromodomain-containing protein 4, 3-methyl-6-(4-methylpiperidin-1-yl)-[1,2,4]triazolo[4,3-b]pyridazine (3 entities in total)
• 機能のキーワード: bromodomain, inhibitor, transcription
• 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: 15330.68

構造登録者

Bader, G.,Kessler, D. (登録日: 2026-07-22, 公開日: 2026-08-05)

主引用文献

Beier, A.,Platzer, G.,Hofurthner, T.,Ptaszek, A.L.,Lichtenecker, R.J.,Geist, L.,Fuchs, J.E.,McConnell, D.B.,Mayer, M.,Konrat, R.
Probing Protein-Ligand Methyl-pi Interaction Geometries through Chemical Shift Measurements of Selectively Labeled Methyl Groups.
J Med Chem, 67:13187-13196, 2024

PubMed Abstract: Fragment-based drug design is heavily dependent on the optimization of initial low-affinity binders. Herein we introduce an approach that uses selective labeling of methyl groups in leucine and isoleucine side chains to directly probe methyl-π contacts, one of the most prominent forms of interaction between proteins and small molecules. Using simple NMR chemical shift perturbation experiments with selected BRD4-BD1 binders, we find good agreement with a commonly used model of the ring-current effect as well as the overall interaction geometries extracted from the Protein Data Bank. By combining both interaction geometries and chemical shift calculations as fit quality criteria, we can position dummy aromatic rings into an AlphaFold model of the protein of interest. The proposed method can therefore provide medicinal chemists with important information about binding geometries of small molecules in fast and iterative matter, even in the absence of high-resolution experimental structures.

PubMed: 39069741
DOI: 10.1039/b508541a

実験手法

X-RAY DIFFRACTION (2.1 Å)