5FNI

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

Summary for 5FNI

• Entry DOI: 10.2210/pdb5fni/pdb
• Related: 5FNG 5FNH 5FNJ 5FNK 5FNL 5FNM
• Descriptor: CARBONIC ANHYDRASE 2, ZINC ION, GLYCEROL, ... (6 entities in total)
• Functional Keywords: lyase, fragments, carbonic anhydrase, metalloprotein
• Biological source: HOMO SAPIENS (HUMAN)
• Total number of polymer chains: 1
• Total formula weight: 29768.76

Authors

Woods, L.A.,Dolezal, O.,Ren, B.,Ryan, J.H.,Peat, T.S.,Poulsen, S.A. (deposition date: 2015-11-15, release date: 2016-03-02, Last modification date: 2024-01-10)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.6 Å)