PXD035628-2

PXD035628 is an original dataset announced via ProteomeXchange.

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

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.

Dataset with its publication pending

submitter keyword: Protein folding

Structural Perturbation

Disease

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

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2022/11/PXD035628

PRIDE project URI

• PRIDE
  1. PXD035628
     1. Label: PRIDE project
     2. 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