3ELO

Crystal Structure of Human Pancreatic Prophospholipase A2

Summary for 3ELO

• Entry DOI: 10.2210/pdb3elo/pdb
• Descriptor: Phospholipase A2, SULFATE ION (3 entities in total)
• Functional Keywords: human pancreatic prophospholipase a2, trimeric, hydrolase, lipid degradation, metal-binding, secreted
• Biological source: Homo sapiens (human)
• Cellular location: Secreted: P04054
• Total number of polymer chains: 1
• Total formula weight: 14966.86

Authors

Xu, W.,Yi, L.,Feng, Y.,Chen, L.,Liu, J. (deposition date: 2008-09-22, release date: 2009-04-14, Last modification date: 2024-11-13)

Primary citation

Xu, W.,Yi, L.,Feng, Y.,Chen, L.,Liu, J.
Structural insight into the activation mechanism of human pancreatic prophospholipase A2
J.Biol.Chem., 284:16659-16666, 2009

PubMed Abstract: Pancreatic phospholipase A2 (phospholipase A2 group 1B, G1B) belongs to the superfamily of secreted phospholipase A2 (PLA2) enzymes. G1B has been proposed to be a potential target for diseases such as hypertension, obesity, and diabetes. Human pancreatic prophospholipase A2 (pro-hG1B) is activated by cleavage of the first seven-residue propeptide (phospholipase A2 propeptide, PROP). However, questions still remain on the mode of action for pro-hG1B. In this work, we expressed pro-hG1B in Pichia pastoris and determined the crystal structure at 1.55-A resolution. The x-ray structure demonstrates that pro-hG1B forms a trimer. In addition, PROP occupies the catalytic cavity and can be self-cleaved at 37 degrees C. A new membrane-bound surface and activation mechanism are proposed based on the trimeric model of pro-hG1B. We also propose a new autoproteolytic mechanism for pro-hG1B by the reaction triad Asp49-Arg0-Ser(-2) that is similar to the serine protease catalytic triad.

PubMed: 19297324
DOI: 10.1074/jbc.M808029200

Experimental method

X-RAY DIFFRACTION (1.55 Å)