PXD035628 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Structural perturbation at the N-terminal domain of human phosphoglycerate kinase 1 reduces the kinetic stability and unfolding cooperativity of a two-domain enzyme |
Description | Phosphoglycerate kinase has been a model for the stability, folding cooperativity and catalysis of a two-domain protein. The human isoform 1 (hPGK1) is associated with cancer development and rare genetic diseases that affect several of their features. To investigate how mutations affect hPGK1 folding landscape, we have designed and introduced mutations at a buried site in the N-terminal domain (F25 mutants) that either created cavities (F25L, F25V, F25A), enhanced conformational entropy (F25G) or introduced structural strain (F25W) and evaluated their effects using biophysical experimental and theoretical methods. All F25 mutants folded well, but showed reduced unfolding cooperativity, kinetic stability and altered activation energetics according to the results from thermal and chemical denaturation analyses. These alterations correlated well with the structural perturbation caused by mutations and the destabilization caused in the interdomain interface. Importantly, experimental and theoretical analyses showed that these effects are significant even when the perturbation is mild and local based on biophysical and HDX-MS analyses. Our approach will be useful to establish the molecular basis of hPGK1 genotype-phenotype correlations due to phosphorylation events and single amino acid substitutions associated with disease in vitro and inside cells |
HostingRepository | PRIDE |
AnnounceDate | 2023-11-14 |
AnnouncementXML | Submission_2023-11-14_08:57:20.036.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Dmitry Loginov |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | No PTMs are included in the dataset |
Instrument | solariX |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2022-07-29 07:23:46 | ID requested | |
1 | 2022-11-03 04:43:19 | announced | |
⏵ 2 | 2023-11-14 08:57:20 | announced | 2023-11-14: Updated project metadata. |
Publication List
Dataset with its publication pending |
Keyword List
submitter keyword: Protein folding |
Structural Perturbation |
Disease |
Contact List
Petr Man |
contact affiliation | Laboratory of Structural Biology and Cell Signaling Institute of Microbiology of the Czech Acad Sci Prumyslova 595 252 50 Vestec Czech Republic |
contact email | pman@biomed.cas.cz |
lab head | |
Dmitry Loginov |
contact affiliation | BioCeV - Institute of Microbiology of the CAS |
contact email | dloginov@jcu.cz |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD035628
- Label: PRIDE project
- Name: Structural perturbation at the N-terminal domain of human phosphoglycerate kinase 1 reduces the kinetic stability and unfolding cooperativity of a two-domain enzyme