PDBsum entry 2pvs

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protein ligands metals Protein-protein interface(s) links
Hydrolase PDB id
Protein chains
435 a.a. *
SO4 ×8
_CA ×2
Waters ×67
* Residue conservation analysis
PDB id:
Name: Hydrolase
Title: Structure of human pancreatic lipase related protein 2 mutant n336q
Structure: Pancreatic lipase-related protein 2. Chain: a, b. Engineered: yes. Mutation: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: pnliprp2, plrp2. Expressed in: pichia pastoris. Expression_system_taxid: 4922.
3.00Å     R-factor:   0.193     R-free:   0.249
Authors: S.Spinelli,C.Eydoux,F.Carriere,C.Cambillau
Key ref: C.Eydoux et al. (2008). Structure of human pancreatic lipase-related protein 2 with the lid in an open conformation. Biochemistry, 47, 9553-9564. PubMed id: 18702514
10-May-07     Release date:   18-Dec-07    
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Protein chains
Pfam   ArchSchema ?
P54317  (LIPR2_HUMAN) -  Pancreatic lipase-related protein 2
469 a.a.
435 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Enzyme reactions 
   Enzyme class 1: E.C.  - Galactolipase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: 1,2-diacyl-3-beta-D-galactosyl-sn-glycerol + 2 H2O = 3-beta-D- galactosyl-sn-glycerol + 2 carboxylates
+ 2 × H(2)O
= 3-beta-D- galactosyl-sn-glycerol
+ 2 × carboxylates
   Enzyme class 2: E.C.  - Triacylglycerol lipase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Triacylglycerol + H2O = diacylglycerol + a carboxylate
+ 2 × H(2)O
= diacylglycerol
+ 2 × carboxylate
Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular region   2 terms 
  Biological process     small molecule metabolic process   7 terms 
  Biochemical function     catalytic activity     8 terms  


Biochemistry 47:9553-9564 (2008)
PubMed id: 18702514  
Structure of human pancreatic lipase-related protein 2 with the lid in an open conformation.
C.Eydoux, S.Spinelli, T.L.Davis, J.R.Walker, A.Seitova, S.Dhe-Paganon, A.De Caro, C.Cambillau, F.Carrière.
Access to the active site of pancreatic lipase (PL) is controlled by a surface loop, the lid, which normally undergoes conformational changes only upon addition of lipids or amphiphiles. Structures of PL with their lids in the open and functional conformation have required cocrystallization with amphiphiles. Here we report two crystal structures of wild-type and unglycosylated human pancreatic lipase-related protein 2 (HPLRP2) with the lid in an open conformation in the absence of amphiphiles. These structures solved independently are strikingly similar, with some residues of the lid being poorly defined in the electron-density map. The open conformation of the lid is however different from that previously observed in classical liganded PL, suggesting different kinetic properties for HPLRP2. Here we show that the HPLRP2 is directly inhibited by E600, does not present interfacial activation, and acts preferentially on substrates forming monomers or small aggregates (micelles) dispersed in solution like monoglycerides, phospholipids and galactolipids, whereas classical PL displays reverse properties and a high specificity for unsoluble substrates like triglycerides and diglycerides forming oil-in-water interfaces. These biochemical properties imply that the lid of HPLRP2 is likely to spontaneously adopt in solution the open conformation observed in the crystal structure. This open conformation generates a large cavity capable of accommodating the digalactose polar head of galactolipids, similar to that previously observed in the active site of the guinea pig PLRP2, but absent from the classical PL. Most of the structural and kinetic properties of HPLRP2 were found to be different from those of rat PLRP2, the structure of which was previously obtained with the lid in a closed conformation. Our findings illustrate the essential role of the lid in determining the substrate specificity and the mechanism of action of lipases.

Literature references that cite this PDB file's key reference

  PubMed id Reference
19957260 G.Labar, C.Bauvois, F.Borel, J.L.Ferrer, J.Wouters, and D.M.Lambert (2010).
Crystal structure of the human monoacylglycerol lipase, a key actor in endocannabinoid signaling.
  Chembiochem, 11, 218-227.
PDB code: 3hju
20193096 I.A.Brownlee, D.J.Forster, M.D.Wilcox, P.W.Dettmar, C.J.Seal, and J.P.Pearson (2010).
Physiological parameters governing the action of pancreatic lipase.
  Nutr Res Rev, 23, 146-154.  
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