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Interaction Of Platelet Activating Factor Acetyl Hydrolase (Paf Ah) Enzyme In Gln281 To Arg281 Mutation Toward Paf And Its Molecular Dynamic Jayarani Fatimah Putri; widodo .; Muhammad Saifur Rohman
Journal of Tropical Life Science Vol. 4 No. 1 (2014)
Publisher : Journal of Tropical Life Science

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Abstract

Platelet Activating Factor Acetyl Hydrolase (PAF AH) or LpPLA2 is key enzyme in myocardial infarction catalyzes the sn-2 acetyl group of Platelet Activating Factor (PAF) into lyso PAF and acetate as non-potent inflammatory molecules. PAF AH plays a critical role in arterial plaque development of Coronary Artery Disease (CAD). A crystal structure of PAF AH complexes with other ligand and effects of amino acid alteration to protein plasma consequence have also been reported. Here we report on the result of molecular docking and Molecular dynamic (MD) simulation carried out for PAF AH wild type (WT)/PAF and mutant Q281R/PAF complexes. Docking result shown that amino acid residues on active site of Q281 PAF AH mutant have not recognized on PAF AH. Eelectrostatics and hydrophobic bonds significantly reduced in Q281R than wild type. In the 7500 ps MD simulation Q281R showed less dynamics than WT but enzymatic machinary of mutant Q281R was not interrupted during MD simulation as well as PAF AH wildtype. These findings clearly indicated the importance effect of mutant Q281R in PAF AH recognition to its substrate
Lipoprotein-Associated Phospholipase A2 Activity increase the Sensitivity of Framingham Score for detecting the incidence of Acute Myocardial Infarction in sub-population of Indonesian Male Patients Andi Wahjono; Saifur Rohman; Miryanti Cahyaningtias; Rina Yudha; Yanna Indrayana; Mifetika lukitasari; Rusdianto Rusdianto; Aditya Kurniawan; Djanggan Sargowo; Sasmojo Widito; Dadang Hendrawan; Jayarani Fatimah Putri; widodo Ph.D
Journal of Global Pharma Technology Vol. 9 Issue 7 : 2017
Publisher : Journal of Global Pharma Technology

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Abstract

Background: Lipoprotein-associated phospholipase A2 (Lp-PLA2) is an inflammatory biomarker of cardiovascular disease. Framingham score is currently a widely used risk stratification tool for detecting the incidence of acute myocardial infarction (AMI), although it is not very sensitive. Adding Lp-PLA2 to the Framingham score can raise the odds ratio (OR) for AMI, but requires further research.Objectives: In this study, we examine the role of Lp-PLA2 in increasing the sensitivity of the Framingham score for detecting the incidence of AMI.Methods: This study was a case-control study of 97 male patients, 60 of whom had AMI and were treated in the intensive care unit as test subjects, and 37 of whom were non-AMI patients with normal treadmill test used as controls.Results:Lp-PLA2 activity was found to be higher in the AMI group than that in the control group (83.97 ± 27.15 nmol/ml/min vs. 55.04 ± 31.99 nmol/ml/min). Eighteen patients (30%) with AMI were included in the high-risk category according to the Framingham score; this number increased to 36 patients after the addition of Lp-PLA2 activity to the Framingham score. Analysis using a receiver operating characteristic (ROC) showed a cut-off value for Lp-PLA2 activity associated with AMI of approximately 74.21 nmol/ml/min with an accuracy of 67%. The OR for detecting AMI incidence increased after the addition of Lp-PLA2 activity from 1:01 (CI 95%, 0.414–2.48) to 4.67 (CI 95%, 1.88-11.61).Conclusions:   The addition of Lp-PLA2 activity may increase the sensitivity of the Framingham score for detecting the incidence of AMI.