6P2U

Structure of Mortalin-NBD with N6-propargyladenosine-5'-diphosphate

Summary for 6P2U

• Entry DOI: 10.2210/pdb6p2u/pdb
• Related: 4KBO 6NHK
• Descriptor: Stress-70 protein, mitochondrial, 9-{5-O-[(S)-hydroxy(phosphonooxy)phosphoryl]-alpha-D-ribofuranosyl}-N-(prop-2-yn-1-yl)-9H-purin-6-amine, PHOSPHATE ION, ... (5 entities in total)
• Functional Keywords: inhibitor, complex, atpase, chaperone
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 42000.59

Authors

Moseng, M.A.,Page, R.C. (deposition date: 2019-05-22, release date: 2019-06-19, Last modification date: 2023-10-11)

Primary citation

Moseng, M.A.,Nix, J.C.,Page, R.C.
2- and N6-functionalized adenosine-5'-diphosphate analogs for the inhibition of mortalin.
Febs Lett., 593:2030-2039, 2019

PubMed 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.

PubMed: 31177526
DOI: 10.1002/1873-3468.13475

Experimental method

X-RAY DIFFRACTION (2 Å)