Human Group IIA Phospholipase A<sub>2</sub>—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
Affiliations
Kieran F. Scott
School of Medicine, Western Sydney University, Campbelltown, NSW 2560, Australia
Timothy J. Mann
School of Medicine, Western Sydney University, Campbelltown, NSW 2560, Australia
Shadma Fatima
School of Medicine, Western Sydney University, Campbelltown, NSW 2560, Australia
Mila Sajinovic
Ingham Institute of Applied Medical Research, Liverpool, NSW 2170, Australia
Anshuli Razdan
Ingham Institute of Applied Medical Research, Liverpool, NSW 2170, Australia
Ryung Rae Kim
School of Pharmacy, Faculty of Medicine and Health, University of Sydney, Sydney, NSW 2006, Australia
Adam Cooper
School of Medicine, Western Sydney University, Campbelltown, NSW 2560, Australia
Aflah Roohullah
School of Medicine, Western Sydney University, Campbelltown, NSW 2560, Australia
Katherine J. Bryant
School of Photovoltaic and Renewable Energy Engineering, UNSW Sydney, Sydney, NSW 2052, Australia
Kasuni K. Gamage
School of Science, Western Sydney University, Campbelltown, NSW 2560, Australia
David G. Harman
School of Science, Western Sydney University, Campbelltown, NSW 2560, Australia
Fatemeh Vafaee
School of Biotechnology and Biological Sciences, University of New South Wales (UNSW Sydney), Sydney, NSW 2052, Australia
Garry G. Graham
Department of Clinical Pharmacology, St Vincent’s Hospital Sydney, Darlinghurst, NSW 2010, Australia
W. Bret Church
School of Pharmacy, Faculty of Medicine and Health, University of Sydney, Sydney, NSW 2006, Australia
Pamela J. Russell
Australian Prostate Cancer Research Centre—QUT, Brisbane, QLD 4102, Australia
Qihan Dong
Chinese Medicine Anti-Cancer Evaluation Program, Greg Brown Laboratory, Central Clinical School and Charles Perkins Centre, The University of Sydney, Sydney, NSW 2006, Australia
Paul de Souza
School of Medicine, Western Sydney University, Campbelltown, NSW 2560, Australia
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.
