PXD072585-1

PXD072585 is an original dataset announced via ProteomeXchange.

Title	Structural dynamics of staphylokinase thrombolytics studied at different time-scales
Description	Cardiovascular diseases, including ischemic stroke, necessitate improved thrombolytic agents. Staphylokinase (SAK), a microbe-encoded plasminogen activator, is a promising alternative to the widely used tissue plasminogen activator (tPA) due to its high fibrin specificity and low production cost. Yet, its use in clinical settings is hampered by an immunogenicity issue. To overcome this, non-immunogenic variants, SAK-SY155 and SAK-THR174, were engineered. However, the molecular basis underlying their reduced immunogenicity is puzzling and requires detailed elucidation. In this work, we determine molecular structures and compare dynamical behaviour between non-immunogenic and immunogenic SAK variants, using a combination of experimental and computational structural techniques. All variants share the canonical SAK fold and retain similar plasminogen activation kinetics, despite the number of introduced substitutions. Crucially, the non-immunogenic variants exhibit distinct dynamic profiles, with SAK-THR174 showing substantially increased flexibility in the H1 helix and B3 region. Similarly, SAK-SY155 exhibits an increased flexibility in the H1-B3 loop and propensity to homodimerize. These dynamic changes are found in the known immunogenic hotspots. Our multi-scale dynamics analysis thus provides the molecular explanation for the reduced immunogenicity and altered thermostability of the engineered variants, without compromising their fibrinolytic function. This information is critical for the design of next-generation thrombolytics.
HostingRepository	PRIDE
AnnounceDate	2026-09-09
AnnouncementXML	Submission_2026-09-09_10:39:09.041.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Naina Verma
SpeciesList	scientific name: Escherichia coli; NCBI TaxID: NEWT:562;
ModificationList	No PTMs are included in the dataset
Instrument	Bruker Daltonics timsTOF series

Revision	Datetime	Status	ChangeLog Entry
0	2026-01-02 10:32:40	ID requested
⏵ 1	2026-09-09 10:39:09	announced

Dataset with its publication pending

submitter keyword: thrombolysis

staphylokinase

immunogenicity

molecular structure

protein dynamics

HDX

mass spectrometry

Prof Lenka Hernychova
contact affiliation	RECAMO, Masaryk Memorial Cancer Institute Zluty Kopec, Brno Czech Republic
contact email	Lenka.hernychova@mou.cz
lab head
Naina Verma
contact affiliation	Masaryk Memorial Cancer Institute
contact email	naina.verma@mou.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/2026/09/PXD072585

PRIDE project URI

• PRIDE
  1. PXD072585
     1. Label: PRIDE project
     2. Name: Structural dynamics of staphylokinase thrombolytics studied at different time-scales