PDBsum entry 6o2e

Transcription

PDB id: 6o2e

Contents

Protein chain

32 a.a.

Waters ×42

PDB id:

6o2e

Name:

Transcription

Title:

Gcn4 with asparagine at position 18

Structure:

General control protein gcn4. Chain: a. Synonym: amino acid biosynthesis regulatory protein. Engineered: yes. Mutation: yes

Source:

Synthetic: yes. Saccharomyces cerevisiae (strain atcc 204508 / s288c). Baker's yeast. Organism_taxid: 559292

Resolution:

1.90Å R-factor: 0.218 R-free: 0.247

Authors:

S.R.E.Draper,Q.Xiao,M.Smith,J.L.Price

Key ref:

Q.Xiao et al. (2019). Influence of PEGylation on the Strength of Protein Surface Salt Bridges. ACS Chem Biol, 14, 1652-1659. PubMed id: 31188563 DOI: 10.1021/acschembio.9b00432

Date:

22-Feb-19 Release date: 26-Jun-19

Protein chain

P03069  (GCN4_YEAST) -  General control transcription factor GCN4 from Saccharomyces cerevisiae (strain ATCC 204508 / S288c)

Seq: 281 a.a.

Struc: 31 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

DOI no: 10.1021/acschembio.9b00432

ACS Chem Biol 14:1652-1659 (2019)

PubMed id: 31188563

Influence of PEGylation on the Strength of Protein Surface Salt Bridges.

Q.Xiao, S.R.E.Draper, M.S.Smith, N.Brown, N.A.B.Pugmire, D.S.Ashton, A.J.Carter, E.E.K.Lawrence, J.L.Price.

ABSTRACT

Conjugation of polyethylene glycol (PEGylation) is a well-known strategy for extending the serum half-life of protein drugs and for increasing their resistance to proteolysis and aggregation. We previously showed that PEGylation can increase protein conformational stability; the extent of PEG-based stabilization depends on the PEGylation site, the structure of the PEG-protein linker, and the ability of PEG to release water molecules from the surrounding protein surface to the bulk solvent. The strength of a noncovalent interaction within a protein depends strongly on its microenvironment, with salt-bridge and hydrogen-bond strength increasing in nonpolar versus aqueous environments. Accordingly, we wondered whether partial desolvation by PEG of the surrounding protein surface might result in measurable increases in the strength of a salt bridge near a PEGylation site. Here we explore this possibility using triple-mutant box analysis to assess the impact of PEGylation on the strength of nearby salt bridges at specific locations within three peptide model systems. The results indicate that PEG can increase the nearby salt-bridge strength, though this effect is not universal, and its precise structural prerequisites are not a simple function of secondary structural context, of the orientation and distance between the PEGylation site and salt bridge, or of salt-bridge residue identity. We obtained high-resolution X-ray diffraction data for a PEGylated peptide in which PEG enhances the strength of a nearby salt bridge. Comparing the electron density map of this PEGylated peptide versus that of its non-PEGylated counterpart provides evidence of localized protein surface desolvation as a mechanism for PEG-based salt-bridge stabilization.