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PXD035628

PXD035628 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleStructural perturbation at the N-terminal domain of human phosphoglycerate kinase 1 reduces the kinetic stability and unfolding cooperativity of a two-domain enzyme
DescriptionPhosphoglycerate 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
HostingRepositoryPRIDE
AnnounceDate2022-11-03
AnnouncementXMLSubmission_2022-11-03_04:43:18.917.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterDmitryLoginov
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListNo PTMs are included in the dataset
InstrumentsolariX
Dataset History
RevisionDatetimeStatusChangeLog Entry
02022-07-29 07:23:46ID requested
12022-11-03 04:43:19announced
Publication List
Keyword List
submitter keyword: Protein folding
Structural Perturbation
Disease
Contact List
PetrMan
contact affiliationLaboratory of Structural Biology and Cell Signaling Institute of Microbiology of the Czech Acad Sci Prumyslova 595 252 50 Vestec Czech Republic
contact emailpman@biomed.cas.cz
lab head
DmitryLoginov
contact affiliationBioCeV - Institute of Microbiology of the CAS
contact emaildloginov@jcu.cz
dataset submitter
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Dataset FTP location
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