1OP8

Crystal Structure of Human Granzyme A

1OP8 の概要

• エントリーDOI: 10.2210/pdb1op8/pdb
• 分子名称: Granzyme A, SULFATE ION (3 entities in total)
• 機能のキーワード: granzyme a, serine proteinase, apoptosis, hydrolase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Isoform alpha: Secreted: P12544
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 156283.09

構造登録者

Hink-Schauer, C.,Estebanez-Perpina, E.,Bode, W.,Jenne, D. (登録日: 2003-03-05, 公開日: 2003-07-01, 最終更新日: 2024-10-30)

主引用文献

Hink-Schauer, C.,Estebanez-Perpina, E.,Kurschus, F.,Bode, W.,Jenne, D.
Crystal structure of the apoptosis-inducing human granzyme A dimer
NAT.STRUCT.BIOL., 10:535-540, 2003

PubMed Abstract: Granzyme A (GzmA) belongs to a family of trypsin-like serine proteases localized in cytoplasmic granules of activated lymphocytes and natural killer (NK) cells. In contrast to the related granzyme B (GzmB), GzmA forms a stable disulfide-linked homodimer and triggers target-cell death in a caspase-independent way. Limited proteolysis of a high-molecular-mass complex containing SET (also named putative HLA-associated protein II or PHAPII), PHAPI (pp32, leucine-rich acidic nuclear protein) and HMG2 by GzmA liberates NM23-H1, a Mg2+-dependent DNase that causes single-stranded breaks in nuclear DNA. By analyzing the dimeric GzmA structure at a resolution of 2.5 A, we determined the substrate-binding constraints and selective advantages of the two domains arranged as a unique functional tandem. The active sites of the two subunits point in opposite directions and the nearby noncatalytic surfaces can function as exosites, presenting substrates to the active site region of the adjacent partner in a manner analogous to staphylokinase or streptokinase, which present plasminogen to the cofactor-plasmin and cofactor-plasminogen complexes.

PubMed: 12819770
DOI: 10.1038/nsb945

実験手法

X-RAY DIFFRACTION (2.5 Å)