PDBsum entry 5iz5

Hydrolase

PDB id: 5iz5

Contents

Protein chains

746 a.a.

Ligands

SO4 ×14

Waters ×432

PDB id:

5iz5

Name:

Hydrolase

Title:

Human givd cytosolic phospholipase a2

Structure:

Cytosolic phospholipase a2 delta. Chain: b, a. Fragment: unp residues 2-810. Synonym: cpla2-delta,phospholipase a2 group ivd. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: pla2g4d. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108.

Resolution:

2.20Å R-factor: 0.224 R-free: 0.238

Authors:

H.Wang,M.G.Klein

Key ref:

H.Wang et al. (2016). Structure of Human GIVD Cytosolic Phospholipase A2 Reveals Insights into Substrate Recognition. J Mol Biol, 428, 2769-2779. PubMed id: 27220631 DOI: 10.1016/j.jmb.2016.05.012

Date:

24-Mar-16 Release date: 08-Jun-16

Protein chains

Q86XP0  (PA24D_HUMAN) -  Cytosolic phospholipase A2 delta from Homo sapiens

Seq: 818 a.a.

Struc: 746 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: 10.1016/j.jmb.2016.05.012

J Mol Biol 428:2769-2779 (2016)

PubMed id: 27220631

Structure of Human GIVD Cytosolic Phospholipase A2 Reveals Insights into Substrate Recognition.

H.Wang, M.G.Klein, G.Snell, W.Lane, H.Zou, I.Levin, K.Li, B.C.Sang.

ABSTRACT

Cytosolic phospholipases A2 (cPLA2s) consist of a family of calcium-sensitive enzymes that function to generate lipid second messengers through hydrolysis of membrane-associated glycerophospholipids. The GIVD cPLA2 (cPLA2δ) is a potential drug target for developing a selective therapeutic agent for the treatment of psoriasis. Here, we present two X-ray structures of human cPLA2δ, capturing an apo state, and in complex with a substrate-like inhibitor. Comparison of the apo and inhibitor-bound structures reveals conformational changes in a flexible cap that allows the substrate to access the relatively buried active site, providing new insight into the mechanism for substrate recognition. The cPLA2δ structure reveals an unexpected second C2 domain that was previously unrecognized from sequence alignments, placing cPLA2δ into the class of membrane-associated proteins that contain a tandem pair of C2 domains. Furthermore, our structures elucidate novel inter-domain interactions and define three potential calcium-binding sites that are likely important for regulation and activation of enzymatic activity. These findings provide novel insights into the molecular mechanisms governing cPLA2's function in signal transduction.