1OP8

Crystal Structure of Human Granzyme A

Summary for 1OP8

• Entry DOI: 10.2210/pdb1op8/pdb
• Descriptor: Granzyme A, SULFATE ION (3 entities in total)
• Functional Keywords: granzyme a, serine proteinase, apoptosis, hydrolase
• Biological source: Homo sapiens (human)
• Cellular location: Isoform alpha: Secreted: P12544
• Total number of polymer chains: 6
• Total formula weight: 156283.09

Authors

Hink-Schauer, C.,Estebanez-Perpina, E.,Bode, W.,Jenne, D. (deposition date: 2003-03-05, release date: 2003-07-01, Last modification date: 2024-10-30)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.5 Å)