The molecular basis of Human FN3K mediated phosphorylation of glycated substrates

Ankur Garg, Kin Fan On, Yang Xiao, Elad Elkayam, Paolo Cifani, Yael David and Leemor Joshua-Tor ()
Additional contact information
Ankur Garg: Cold Spring Harbor
Kin Fan On: Cold Spring Harbor
Yang Xiao: Memorial Sloan Kettering Cancer Center
Elad Elkayam: Cold Spring Harbor
Paolo Cifani: Cold Spring Harbor
Yael David: Memorial Sloan Kettering Cancer Center
Leemor Joshua-Tor: Cold Spring Harbor

Nature Communications, 2025, vol. 16, issue 1, 1-14

Abstract: Abstract Glycation, a non-enzymatic post-translational modification occurring on proteins, can be actively reversed via site-specific phosphorylation of the fructose-lysine moiety by FN3K kinase, to impact the cellular function of the target protein. A regulatory axis between FN3K and glycated protein targets has been associated with conditions like diabetes and cancer. However, the molecular basis of this relationship has not been explored so far. Here, we determined a series of crystal structures of HsFN3K in the apo-state, and in complex with different nucleotide analogs together with a sugar substrate mimic to reveal the features important for its kinase activity and substrate recognition. Additionally, the dynamics in sugar substrate binding during the kinase catalytic cycle provide important mechanistic insights into HsFN3K function. Our structural work provides the molecular basis for rational small molecule design targeting FN3K.

Date: 2025
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-025-56207-z Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-56207-z

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-025-56207-z

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().