Site-specific .epsilon.-amino monoacylation of pancreatic phospholipase A2. 2. Transformation of soluble phospholipase A2 into a highly penetrating "membrane-bound" form

Biochemistry ◽  
1988 ◽  
Vol 27 (5) ◽  
pp. 1688-1694 ◽  
Author(s):  
Frans C. Van der Wiele ◽  
Wim Atsma ◽  
Ben Roelofsen ◽  
Margreet Van Linde ◽  
Jan Van Binsbergen ◽  
...  
2009 ◽  
Vol 284 (24) ◽  
pp. 16659-16666 ◽  
Author(s):  
Wei Xu ◽  
Lina Yi ◽  
Yumei Feng ◽  
Ling Chen ◽  
Jinsong Liu

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-Å 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 °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.


Biochemistry ◽  
1988 ◽  
Vol 27 (5) ◽  
pp. 1683-1688 ◽  
Author(s):  
Frans C. Van der Wiele ◽  
Wim Atsma ◽  
Ruud Dijkman ◽  
Antoine M. M. Schreurs ◽  
Arend J. Slotboom ◽  
...  

2001 ◽  
Vol 20 (3) ◽  
pp. 149-157 ◽  
Author(s):  
Asim K. Mandal ◽  
Zhongjian Zhang ◽  
Janice Y. Chou ◽  
Drazen Zimonjic ◽  
Catherine L. Keck ◽  
...  

Biochemistry ◽  
2000 ◽  
Vol 39 (19) ◽  
pp. 5702-5711 ◽  
Author(s):  
Bao-Zhu Yu ◽  
Marcel J. W. Janssen ◽  
Hubertus M. Verheij ◽  
Mahendra Kumar Jain

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