Human group III PLA2 as a drug target: structural analysis and inhibitor binding studies

International Journal of Biological Macromolecules
Gururao HariprasadRamaswamy Prem Kumar

Abstract

Group III phospholipase A(2) is a known mediator of inflammation, atherosclerosis and cancer in mammals. This enzyme, therefore, is a potential drug target. The availability of the human group III phospholipase A(2) (hIIIPLA(2)) amino acid sequence offers an opportunity to study its structural features by modeling. The monomeric hIII PLA(2) model is based on the 44% identity it has with the bee venom PLA(2), the only known representative structure of this group. The overall structure comprises of three α-helices, a β-wing and the calcium binding loop which is present at the N-terminus of the enzyme. However, the unique structural features of hIIIPLA(2) in comparison to the other well known group I/II PLA(2)s are: (1) the replacement of the 'conserved' tyrosine residue by phenylalanine at position 87 in the active site; (2) a decrease in the volume of the substrate binding hydrophobic channel and (3) presence of a C-terminal extension which has a close proximity to the third helix. Docking studies of the enzyme with small molecules gives a detailed insight into the participating residues of the enzyme and also the possible type of interactions with the drug molecules. The ligand molecules have binding affinities predicted to ran...Continue Reading

References

Dec 1, 1990·Protein Engineering·O P KuipersG H de Haas
Mar 14, 2000·The Journal of Biological Chemistry·E ValentinG Lambeau
Nov 18, 2000·Biochimica Et Biophysica Acta·D A Six, E A Dennis
Feb 12, 2002·Bioinformatics·Christophe CombetChristophe Geourjon
Sep 10, 2002·Bioinformatics·Christophe LambertEric Depiereux
Dec 14, 2002·Journal of Molecular Graphics & Modelling·C M VenkatachalamM Waldman
Jul 16, 2003·Clinical and Experimental Pharmacology & Physiology·Supath SrisawatYupin Sanvarinda
Apr 7, 2004·European Journal of Biochemistry·Norma A Valdez-CruzLourival D Possani
Nov 5, 2005·Toxicon : Official Journal of the International Society on Toxinology·Talat JabeenT P Singh
Nov 23, 2005·Bioinformatics·Konstantin ArnoldTorsten Schwede
Jun 5, 2007·Seminars in Cutaneous Medicine and Surgery·Luis Requena, Evaristo Sánchez Yus
Feb 28, 2009·Nature Protocols·Lawrence A Kelley, Michael J E Sternberg
Apr 18, 2009·The Biochemical Journal·Hiroyasu SatoMakoto Murakami

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Citations

Jun 25, 2013·Journal of Molecular Modeling·Gururao HariprasadReema Singh
Oct 10, 2014·Indian Journal of Clinical Biochemistry : IJCB·Gururao HariprasadSouparno Adhikary
Mar 20, 2012·Journal of Enzyme Inhibition and Medicinal Chemistry·Maja RadisavljevićMarijana Petković
Apr 13, 2011·Metallomics : Integrated Biometal Science·Marijana Petković, Tina Kamčeva
Sep 29, 2020·Journal of Inflammation Research·Mohd Imran Khan, Gururao Hariprasad
Dec 29, 2020·Journal of Inflammation Research·Mohd Imran Khan, Gururao Hariprasad

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