6B7C

Crystal structure of E.coli Phosphopantetheine Adenylyltransferase (PPAT/CoaD) in complex with N-((1,3-dimethyl-1H-pyrazol-5-yl)methyl)-5-methyl-1H-imidazo[4,5-b]pyridin-2-amine

6B7C の概要

• エントリーDOI: 10.2210/pdb6b7c/pdb
• 分子名称: Phosphopantetheine adenylyltransferase, N-[(1,3-dimethyl-1H-pyrazol-5-yl)methyl]-5-methyl-3H-imidazo[4,5-b]pyridin-2-amine, SULFATE ION, ... (7 entities in total)
• 機能のキーワード: coad, transferase
• 由来する生物種: Escherichia coli (strain K12)
• 細胞内の位置: Cytoplasm : P0A6I6
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 39606.99

構造登録者

Proudfoot, A.W.,Bussiere, D.,Lingel, A. (登録日: 2017-10-03, 公開日: 2017-12-27, 最終更新日: 2023-10-04)

主引用文献

Proudfoot, A.,Bussiere, D.E.,Lingel, A.
High-Confidence Protein-Ligand Complex Modeling by NMR-Guided Docking Enables Early Hit Optimization.
J. Am. Chem. Soc., 139:17824-17833, 2017

PubMed Abstract: Structure-based drug design is an integral part of modern day drug discovery and requires detailed structural characterization of protein-ligand interactions, which is most commonly performed by X-ray crystallography. However, the success rate of generating these costructures is often variable, in particular when working with dynamic proteins or weakly binding ligands. As a result, structural information is not routinely obtained in these scenarios, and ligand optimization is challenging or not pursued at all, representing a substantial limitation in chemical scaffolds and diversity. To overcome this impediment, we have developed a robust NMR restraint guided docking protocol to generate high-quality models of protein-ligand complexes. By combining the use of highly methyl-labeled protein with experimentally determined intermolecular distances, a comprehensive set of protein-ligand distances is generated which then drives the docking process and enables the determination of the correct ligand conformation in the bound state. For the first time, the utility and performance of such a method is fully demonstrated by employing the generated models for the successful, prospective optimization of crystallographically intractable fragment hits into more potent binders.

PubMed: 29190085
DOI: 10.1021/jacs.7b07171

実験手法

X-RAY DIFFRACTION (1.564 Å)