PDBsum entry 2oxe

Hydrolase

PDB id: 2oxe

Contents

Protein chains

435 a.a. *

Ligands

NAG-NAG-MAN-MAN-MAN ×2

Metals

_CL ×5

_CA ×2

Waters ×76

* Residue conservation analysis

PDB id:

2oxe

Name:

Hydrolase

Title:

Structure of the human pancreatic lipase-related protein 2

Structure:

Pancreatic lipase-related protein 2. Chain: a, b. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Tissue: pancreas. Gene: pnliprp2, plrp2. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108.

Resolution:

2.80Å R-factor: 0.224 R-free: 0.261

Authors:

J.R.Walker,T.Davis,A.Seitova,P.J.Finerty Jr.,C.Butler-Cole, I.Kozieradzki,J.Weigelt,M.Sundstrom,C.H.Arrowsmith,A.M.Edwards, A.Bochkarev,S.Dhe-Paganon,Structural Genomics Consortium (Sgc)

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

Date:

20-Feb-07 Release date: 27-Mar-07

Protein chains

P54317  (LIPR2_HUMAN) -  Pancreatic lipase-related protein 2 from Homo sapiens

Seq: 469 a.a.

Struc: 435 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class 1: E.C.3.1.1.26 - galactolipase.
• Reaction: a 1,2-diacyl-3-O-(beta-D-galactosyl)-sn-glycerol + 2 H2O = 3-beta-D- galactosyl-sn-glycerol + 2 a fatty acid + 2 H⁺

1,2-diacyl-3-O-(beta-D-galactosyl)-sn-glycerol + 2 × H2O = 3-beta-D- galactosyl-sn-glycerol (Bound ligand (Het Group name = MAN) matches with 64.71% similarity) + 2 × a fatty acid + 2 × H(+)

• Enzyme class 2: E.C.3.1.1.3 - triacylglycerol lipase.
• Reaction: a triacylglycerol + H2O = a diacylglycerol + a fatty acid + H⁺

triacylglycerol + 2 × H2O = diacylglycerol (Bound ligand (Het Group name = MAN) matches with 43.75% similarity) + 2 × fatty acid + 2 × H(+)

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

reference

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.

ABSTRACT

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.