Human Group IIA Phospholipase A2 : three decades on from its discovery

Kieran F. Scott, Timothy J. Mann, Shadma Fatima, Mila Sajinovic, Anshuli Razdan, Ryung Rae Kim, Adam Cooper, Aflah Roohullah, Katherine J. Bryant, Kasuni K. Gamage, David G. Harman, Fatemeh Vafaee, Garry G. Graham, W. Bret Church, Pamela J. Russell, Qihan Dong, Paul de Souza

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)

Abstract

Phospholipase A2 (PLA2) enzymes were first recognized as an enzyme activity class in 1961. The secreted (sPLA2) enzymes were the first of the five major classes of human PLA2s to be identified and now number nine catalytically-active structurally homologous proteins. The best-studied of these, group IIA sPLA2, has a clear role in the physiological response to infection and minor injury and acts as an amplifier of pathological inflammation. The enzyme has been a target for anti-inflammatory drug development in multiple disorders where chronic inflammation is a driver of pathology since its cloning in 1989. Despite intensive effort, no clinically approved medicines targeting the enzyme activity have yet been developed. This review catalogues the major discoveries in the human group IIA sPLA2 field, focusing on features of enzyme function that may explain this lack of success and discusses future research that may assist in realizing the potential benefit of targeting this enzyme. Functionally-selective inhibitors together with isoform-selective inhibitors are necessary to limit the apparent toxicity of previous drugs. There is also a need to define the relevance of the catalytic function of hGIIA to human inflammatory pathology relative to its recently-discovered catalysis-independent function.
Original languageEnglish
Article number7267
Number of pages20
JournalMolecules
Volume26
Issue number23
DOIs
Publication statusPublished - 2021

Open Access - Access Right Statement

© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).

Fingerprint

Dive into the research topics of 'Human Group IIA Phospholipase A2 : three decades on from its discovery'. Together they form a unique fingerprint.

Cite this