Work

2‐ and N6‐functionalized adenosine‐5′‐diphosphate analogs for the inhibition of mortalin

Year: 2019

Type: article

Abstract: Our early efforts to find a covalent inhibitor of mortalin, a member of the 70 kD heat shock protein (Hsp70) family, led us to solve the structure of the mortalin nucleotide-binding domain (NBD) in complex with N6-propargyladenosine-5'-diphosphate. The acquired structure emphasizes the ability of the nucleotide-binding pocket to accommodate modified ADP compounds. A library of ADP analogs modified at either the 2- or N6-positions of adenosine was screened against the mortalin-NBD. Competitive inhibition and binding assays of the analogs demonstrate that modifications at the 2- or N6-positions have potential to bind and inhibit mortalin uniquely compared to other Hsp70 homologs, and that modifications at the 2-position confer the greatest selectivity in binding and inhibition of the mortalin-NBD.

Source: FEBS Letters

DOI: 10.1002/1873-3468.13475

Authors: Mitchell A. Moseng, Jay C. Nix, Richard C. Page

Institutions: Miami University, Lawrence Berkeley National Laboratory, Molecular Biology Consortium, Advanced Light Source

Language: English

Topic: Heat shock proteins research

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: green

Funders: National Science Foundation, University of Miami, National Institutes of Health, National Institute of General Medical Sciences