6R4D

Aurora-A in complex with shape-diverse fragment 58

Summary for 6R4D

• Entry DOI: 10.2210/pdb6r4d/pdb
• Descriptor: Aurora kinase A, ADENOSINE-5'-DIPHOSPHATE, MAGNESIUM ION, ... (6 entities in total)
• Functional Keywords: ser/thr kinase allosteric site, transferase
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 33790.32

Authors

Bayliss, R.,McIntyre, P.J. (deposition date: 2019-03-22, release date: 2019-05-08, Last modification date: 2024-10-23)

Primary citation

Zhang, R.,McIntyre, P.J.,Collins, P.M.,Foley, D.J.,Arter, C.,von Delft, F.,Bayliss, R.,Warriner, S.,Nelson, A.
Construction of a Shape-Diverse Fragment Set: Design, Synthesis and Screen against Aurora-A Kinase.
Chemistry, 25:6831-6839, 2019

PubMed Abstract: Historically, chemists have explored chemical space in a highly uneven and unsystematic manner. As an example, the shape diversity of existing fragment sets does not generally reflect that of all theoretically possible fragments. To assess experimentally the added value of increased three dimensionality, a shape-diverse fragment set was designed and collated. The set was assembled by both using commercially available fragments and harnessing unified synthetic approaches to sp -rich molecular scaffolds. The resulting set of 80 fragments was highly three-dimensional, and its shape diversity was significantly enriched by twenty synthesised fragments. The fragment set was screened by high-throughput protein crystallography against Aurora-A kinase, revealing four hits that targeted the binding site of allosteric regulators. In the longer term, it is envisaged that the fragment set could be screened against a range of functionally diverse proteins, allowing the added value of more shape-diverse screening collections to be more fully assessed.

PubMed: 31026091
DOI: 10.1002/chem.201900815

Experimental method

X-RAY DIFFRACTION (2.009 Å)