Work

Crystallization and crystallographic studies of human serine protease inhibitor (serpin) B9

Year: 2024

Type: article

Abstract: Serine protease inhibitor B9 (serpin B9, also known as protease inhibitor 9 or PI9) plays a critical role in regulating the immune response by specifically inhibiting granzyme B, a serine protease found in cytotoxic T lymphocytes and natural killer cells. Despite its potential as an anticancer drug target, the structural details of serpin B9 have remained elusive until now. In this study, a cleaved form of recombinant human serpin B9 was successfully prepared and crystallized. The crystals belonged to space group P 2 1 2 1 2 1 , with unit-cell parameters a = 68.51, b = 82.32, c = 101.17 Å, and an X-ray diffraction data set was collected at 1.9 Å resolution. The structure shows that serpin B9 adopts a relaxed conformation, with its cleaved reactive-centre loop inserted into the central β-sheet. Unlike other serpins, serpin B9 shows significant structural deviations around helix D, with a larger surface cavity, which could serve as a promising target for small-molecule inhibitors.

Source: Acta Crystallographica Section F Structural Biology Communications

DOI: 10.1107/s2053230x24009439

Authors: Teng Yan, Aiwu Zhou

Institution: Shanghai Jiao Tong University

Language: English

Topic: Enzyme Structure and Function

Subfield: Materials Chemistry

Field: Materials Science

Domain: Physical Sciences

SDG: Good health and well-being

Open Access status: green

Funder: National Natural Science Foundation of China