5FLS

Native state mass spectrometry, surface plasmon resonance and X-ray crystallography correlate strongly as a fragment screening combination

5FLS の概要

• エントリーDOI: 10.2210/pdb5fls/pdb
• 関連するPDBエントリー: 5FLO 5FLP 5FLQ 5FLR 5FLT
• 分子名称: CARBONIC ANHYDRASE 2, ZINC ION, DIMETHYL SULFOXIDE, ... (5 entities in total)
• 機能のキーワード: lyase, fragments, metalloprotein
• 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: 29629.23

構造登録者

Woods, L.A.,Dolezal, O.,Ren, B.,Ryan, J.H.,Peat, T.S.,Poulsen, S.A. (登録日: 2015-10-28, 公開日: 2016-03-02, 最終更新日: 2024-01-10)

主引用文献

Woods, L.,Dolezal, O.,Ren, B.,Ryan, J.H.,Peat, T.S.,Poulsen, S.
Native State Mass Spectrometry, Surface Plasmon Resonance and X-Ray Crystallography Correlate Strongly as a Fragment Screening Combination.
J.Med.Chem., 59:2192-, 2016

PubMed Abstract: Fragment-based drug discovery (FBDD) is contingent on the development of analytical methods to identify weak protein-fragment noncovalent interactions. Herein we have combined an underutilized fragment screening method, native state mass spectrometry, together with two proven and popular fragment screening methods, surface plasmon resonance and X-ray crystallography, in a fragment screening campaign against human carbonic anhydrase II (CA II). In an initial fragment screen against a 720-member fragment library (the "CSIRO Fragment Library") seven CA II binding fragments, including a selection of nonclassical CA II binding chemotypes, were identified. A further 70 compounds that comprised the initial hit chemotypes were subsequently sourced from the full CSIRO compound collection and screened. The fragment results were extremely well correlated across the three methods. Our findings demonstrate that there is a tremendous opportunity to apply native state mass spectrometry as a complementary fragment screening method to accelerate drug discovery.

PubMed: 26882437
DOI: 10.1021/ACS.JMEDCHEM.5B01940

実験手法

X-RAY DIFFRACTION (1.67 Å)