PDBsum entry 1fxf

Hydrolase

PDB id: 1fxf

Contents

Protein chains

124 a.a. *

Ligands

PO4 ×5

MJI

Metals

_CA ×2

Waters ×279

* Residue conservation analysis

PDB id:

1fxf

Name:

Hydrolase

Title:

Carboxylic ester hydrolase complex (dimeric pla2 + mj33 inhibitor + phosphate ions)

Structure:

Phospholipase a2, major isoenzyme. Chain: a, b. Synonym: phosphatidylcholine 2-acylhydrolase, pla2. Engineered: yes

Source:

Sus scrofa. Pig. Organism_taxid: 9823. Expressed in: escherichia coli. Expression_system_taxid: 562

Biol. unit:

Dimer (from PQS)

Resolution:

1.85Å R-factor: 0.161 R-free: 0.268

Authors:

Y.H.Pan,T.M.Epstein,M.K.Jain,B.J.Bahnson

Key ref:

Y.H.Pan et al. (2001). Five coplanar anion binding sites on one face of phospholipase A2: relationship to interface binding. Biochemistry, 40, 609-617. PubMed id: 11170377 DOI: 10.1021/bi002514g

Date:

25-Sep-00 Release date: 25-Sep-01

Protein chains

P00592  (PA21B_PIG) -  Phospholipase A2, major isoenzyme from Sus scrofa

Seq: 146 a.a.

Struc: 124 a.a.

Enzyme reactions

• Enzyme class: E.C.3.1.1.4 - phospholipase A2.
• Reaction: a 1,2-diacyl-sn-glycero-3-phosphocholine + H2O = a 1-acyl-sn-glycero-3- phosphocholine + a fatty acid + H⁺
• Cofactor: Ca(2+)

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

DOI no: 10.1021/bi002514g

Biochemistry 40:609-617 (2001)

PubMed id: 11170377

Five coplanar anion binding sites on one face of phospholipase A2: relationship to interface binding.

Y.H.Pan, T.M.Epstein, M.K.Jain, B.J.Bahnson.

ABSTRACT

We report the structures of the crystallographic dimer of porcine pancreatic IB phospholipase A(2) (PLA2) with either five sulfate or phosphate anions bound. In each structure, one molecule of a tetrahedral mimic MJ33 [1-hexadecyl-3-(trifluoroethyl)-sn-glycero-2-phosphomethanol] and the five anions are shared between the two subunits of the dimer. The sn-2-phosphate of MJ33 is bound in the active site of one subunit (A), and the alkyl chain extends into the active site slot of the second subunit (B) across the subunit-subunit interface. The two subunits are packed together with a large hydrophobic and desolvated surface buried between them along with the five anions that define a plane. The anions bind by direct contact with two cationic residues (R6 and K10) per subunit and through closer-range H-bonding interactions with other polarizable ligands. These features of the "dimer" suggest that the binding of PLA2 to the anionic groups at the anionic interface may be dominated by coordination through H-bonding with only a partial charge compensation needed. Remarkably, the plane defined by the contact surface is similar to the i-face of the enzyme [Ramirez, F., and Jain, M. K. (1991) Proteins: Struct., Funct., Genet. 9, 229-239], which has been proposed to make contact with the substrate interface for the interfacial catalytic turnover. Additionally, these structures not only offer a view of the active PLA2 complexed to an anionic interface but also provide insight into the environment of the tetrahedral intermediate in the rate-limiting chemical step of the turnover cycle. Taken together, our results offer an atomic-resolution structural view of the i-face interactions of the active form of PLA2 associated to an anionic interface.