PMID: 9822688

 

    Legend: Gene, Sites

Title : Structure and activity of rat pancreatic lipase-related protein 2

Abstract :
  1. The pancreas expresses several members of the lipase gene family including pancreatic triglyceride lipase ( PTL ) and two homologous proteins , pancreatic lipase-related proteins 1 and 2 2 (PLRP1 and PLRP2 )
  2. Despite their similar amino acid sequences , PTL , PLRP1 , and PLRP2 differ in important kinetic properties
  3. PLRP1 has no known activity
  4. PTL and PLRP2 differ in substrate specificity, bile acid inhibition, colipase requirement, and interfacial activation
  5. To begin understanding the structural explanations for these functional differences, we solved the crystal structure of rat (r) PLRP2 and further characterized its kinetic properties
  6. The 1.8 A structure of rPLRP2 , like the tertiary structure of human PTL , has a globular N-terminal domain and a beta-sandwich C-terminal domain
  7. The lid domain occupied the closed position, suggesting that rPLRP2 should show interfacial activation
  8. When we reexamined this issue with tripropionin as substrate, rPLRP2 exhibited interfacial activation
  9. Because the active site topology of rPLRP2 resembled that of human PTL , we predicted and demonstrated that the lipase inhibitors E600 and tetrahydrolipstatin inhibit rPLRP2
  10. Although PTL and rPLRP2 have similar active sites , rPLRP2 has a broader substrate specificity that we confirmed using a monolayer technique
  11. With this assay, we showed for the first time that rPLRP2 prefers phosphatidylglycerol and ethanolamine over phosphatidylcholine
  12. In summary, we confirmed and extended the observation that PLRP2 lipases have a broader substrate specificity than PTL , we demonstrated that PLRP2 lipases show interfacial activation, and we solved the first crystal structure of a PLRP2 lipase that contains a lid domain
Output (sent_index, trigger, protein, sugar, site):
  • 7. occupied, , -, -, domain
Output(Part-Of) (sent_index, protein, site):
  • 10. PTL, sites
  • 10. rPLRP2, sites
  • 12. PLRP2 lipase, domain
  • 6. structure of rPLRP2, domain
*Output_Site_Fusion* (sent_index, protein, sugar, site):

 

 

Protein NCBI ID SENTENCE INDEX
pancreatic lipase-related proteins 1 and 2 84028 1
pancreatic triglyceride lipase 25702 1
PTL 5406 1,2,4,6,9,10,12
2 (PLRP1 84028 1
rPLRP2 117554 7,8,9,10,11
pancreatic lipase-related protein 2 117554 0
PLRP2 117554 1,2,4,5,12
PLRP1 84028 2,3
PLRP2 lipase 117554 12
colipase 25680 4
structure of rPLRP2 117554 6