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Glycerol 3 phosphate acyltransferase (GPAT, EC: 188.8.131.52) is recognized as a key player of cellular acyltransferase metabolism. It catalyzes the chain initiation step leading to triglyceride biosynthesis. The protein sequence of GPAT was retrieved from GenBank. However, a substantial and well defined structure is not available for this sequence. The 3D structure of GPAT was modeled using a template structure (PDB ID: 1K30) obtained from Protein databank (PDB) identified by searching with position specific iterative BLAST (PSI-BLAST). Modeling was performed using Modeller 9v9 and protein model is hence generated. The GPAT protein model was subsequently docked with specific ligands (Glycerol 3 phosphate, Oleyol-CoA) using AutoDock. The binding of inhibitors to the protein model of GPAT has been discussed taking into consideration the enzyme protein-ligand interaction studies. Besides, the molecular dynamics study of GPAT was carried out using prime module of Schrodinger suit which reveals the stability with the interacting ligands. The results obtained from the present bioinformatics based study provides new insights for lifting up the triglyceride biosynthesis in an oleaginuous fungus concomitant with incorporation of unsaturated fatty acids probably be significant from medicinal point of view.
Glycerol 3 Phosphate Acyltransferase (GPAT), Oleaginuous fungus, Modeller, Triglyceride, AutoDock, Gromacs.
Glycerol-3-phosphate acyltransferase (GPAT) catalyzes the transfer of an acyl group from an acyl donor to the sn-1 position of glycerol-3-phosphate. The plant cells contain three types of GPAT, which are located in the chloroplasts, mitochondria and cytoplasm, respectively . Sn-Glycerol-3-phosphate acyltransferase (GPAT) catalyzes the acylation at sn-1 position of glycerol-3-phosphate to produce lysophosphatidic acid (LPA). LPA is an important intermediate for the formation of different types of acyl-lipids, such as extracellular lipid polyesters, storage and membrane lipids . Although, The Production of lysophosphatidic acid (LPA) is the first step in the de novo pathway for glycerol biosynthesis, which is mainly catalyzed by the glycerol-3-phosphate acyltransferase (GPATs;EC184.108.40.206). DHAPAT (EC220.127.116.11) also contributes in a minor way, using dihydroxyacetone phosphate as substrate. Final products and intermediate of the glycerolipid synthesis pathway are the main structural components of cellular membranes  (1 date). LPA is a mitogen that mediates multiple cellular processes including cell proliferation . Although, GPAT is involved in triacylglycerol (TAG) and phospholipid synthesis, catalyzing the first committed step. In order to further investigate the in vivo importance of the dominating mitochondrial variant, GPAT1, Female GPAT1 mice had reduced body weight-gain and adiposity when fed chow diet compared with littermate wild-type controls. Furthermore, GPAT1 females on chow diet showed decreased liver TAG content, plasma cholesterol and TAG levels and increased ex vivo liver fatty acid oxidation and plasma ketone bodies. A correlation between reduced mitochondrial GPAT1 activity and decreased proliferation in splenic T-lymphocytes from aged rates. T-lymphocyte proliferation is inhibited and activation induced apoptosis is increased [5, 6]. Glycerol-3-phosphate acyltransferase is a rate-limiting enzyme in mammalian triacylglycerol biosynthesis. GPAT is a target for the treatment of metabolic disorders associated with high lipid accumulation. Although the molecular basis for GPAT1 activation has been investigated extensively. . However Mammals express four isoforms of GPAT. The mitochondrial isoform GPAT1 may have been the acyltransferase that appeared first in evolution. The hepatopancreas of the crustacean Macrobrachium Borelli has a high capacity for triacylglycerol (TAG) biosynthesis and storage . GPAT catalyzes the initial step in the synthesis of all glycerolipids. It is the committed and rate-limiting step and is redundant in Saccharomyces cerevisiae, mammals, and plants .
The present report reflects molecular dynamics simulation and validation of the GPAT protein shows helpful support for further analysis in docking studies, the docking of GPAT protein with G3P and Oleyol-CoA results in interesting docked model with a super coiled secondary structure of the polypeptide chain of the enzyme protein i.e. glycerol-3-phosphate acyltransferase. This unique feature of GPAT projects its activity towards a positive trend. Hypothetically it is mandatory to keep this model stable so that it can be employed for propagating the work in the reagent-based laboratory (in vivo as well as in vitro) to provide certain platforms for activating GPAT enzyme which may probably be helpful in the elevated biosynthesis of unsaturated fatty acids, ultimately providing a substantial products for pharmaceutically enriched drug molecules.
In summary the polar interactions of G3P (GLU168, GLN230, LYS151) and hydrophobic interaction Oleyol-CoA (VAL139, ALA143, PRO145, LEU180, TYR186, PRO235) are among various biochemically significant amino acids and resulted in the folding mechanism of this pharmaceutically pivotal enzyme leading to specific level of energy of activation for enabling the enzyme to accomplish the same biochemical reaction with rather more potentiality in the due course of time. The data obtained so far may be further useful in monitoring the upgradation of unsaturated fatty acid biosynthesis in the plant tissue culture laboratories. Structure analysis suggests that the size and character of the cavity that is formed from this region determines the specific recognition of acyl chains.
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