2HDU

AmpC beta-lactamase in complex with 2-acetamidothiophene-3-carboxylic acid

2HDU の概要

• エントリーDOI: 10.2210/pdb2hdu/pdb
• 関連するPDBエントリー: 2HDQ 2HDR 2HDS
• 分子名称: Beta-lactamase, 2-(ACETYLAMINO)THIOPHENE-3-CARBOXYLIC ACID, POTASSIUM ION, ... (5 entities in total)
• 機能のキーワード: ampc beta-lactamase fragment-based drug design, hydrolase
• 由来する生物種: Escherichia coli K12
• 細胞内の位置: Periplasm: P00811
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 80791.51

構造登録者

Babaoglu, K.,Shoichet, B.K. (登録日: 2006-06-20, 公開日: 2006-11-07, 最終更新日: 2024-12-25)

主引用文献

Babaoglu, K.,Shoichet, B.K.
Deconstructing fragment-based inhibitor discovery
Nat.Chem.Biol., 2:720-723, 2006

PubMed Abstract: Fragment-based screens test multiple low-molecular weight molecules for binding to a target. Fragments often bind with low affinities but typically have better ligand efficiencies (DeltaG(bind)/heavy atom count) than traditional screening hits. This efficiency, combined with accompanying atomic-resolution structures, has made fragments popular starting points for drug discovery programs. Fragment-based design adopts a constructive strategy: affinity is enhanced either by cycles of functional-group addition or by joining two independent fragments together. The final inhibitor is expected to adopt the same geometry as the original fragment hit. Here we consider whether the inverse, deconstructive logic also applies--can one always parse a higher-affinity inhibitor into fragments that recapitulate the binding geometry of the larger molecule? Cocrystal structures of fragments deconstructed from a known beta-lactamase inhibitor suggest that this is not always the case.

PubMed: 17072304
DOI: 10.1038/nchembio831

実験手法

X-RAY DIFFRACTION (1.49 Å)