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A2M bait region engineering - autoconjugation product cross-link identification and PRM quantification

ABSTRACT: In-gel digest of a cross-linked product band was used to identify an internal isopeptide cross-link formed in A2M TR K704 upon bait region cleavage by trypsin. PRM was used to quantify the thiol ester in native PAGE bands of A2M nEXT and EXT mutants.

INSTRUMENT(S): Orbitrap Eclipse

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Seandean Harwood

LAB HEAD: Jan J. Enghild

PROVIDER: PXD023651 | Pride | 2021-09-10

REPOSITORIES: Pride

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Development of selective protease inhibitors via engineering of the bait region of human α<sub>2</sub>-macroglobulin.

Harwood Seandean Lykke SL Nielsen Nadia Sukusu NS Diep Khang K Jensen Kathrine Tejlgård KT Nielsen Peter Kresten PK Yamamoto Kazuhiro K Enghild Jan J JJ

The Journal of biological chemistry 20210615 1

Human α<sub>2</sub>-macroglobulin (A2M) is an abundant protease inhibitor in plasma, which regulates many proteolytic processes and is involved in innate immunity. A2M's unique protease-trapping mechanism of inhibition is initiated when a protease cleaves within the exposed and highly susceptible "bait region." As the wild-type bait region is permissive to cleavage by most human proteases, A2M is accordingly a broad-spectrum protease inhibitor. In this study, we extensively modified the bait reg ...[more]

PMID: 34139236

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