The molecular basis of Human FN3K mediated phosphorylation of glycated substrate

Garg, Ankur, On, Kin Fan, Xiao, Yang, Elkayam, Elad, Cifani, Paolo, David, Yael, Joshua-Tor, Leemor (August 2024) The molecular basis of Human FN3K mediated phosphorylation of glycated substrate. bioRxiv. (Public Dataset) (Submitted)

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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 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 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 rationale small molecule design targeting FN3K.

Item Type: Paper
Subjects: bioinformatics
bioinformatics > genomics and proteomics > genetics & nucleic acid processing
bioinformatics > genomics and proteomics
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification
CSHL Authors:
Communities: CSHL labs > Joshua-Tor lab
CSHL labs > Cifani lab
SWORD Depositor: CSHL Elements
Depositing User: CSHL Elements
Date: 5 August 2024
Date Deposited: 19 Aug 2024 12:50
Last Modified: 19 Aug 2024 12:50
PMCID: PMC11326186
Related URLs:
Dataset ID:
  • Protein Data Bank: 9CX8
  • Protein Data Bank: 9CXV
  • Protein Data Bank: 9CXW
  • Protein Data Bank: 9CXM
  • Protein Data Bank: 9CXN
  • Protein Data Bank: 9CXO
URI: https://repository.cshl.edu/id/eprint/41635

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