scholarly journals Three Dimensional Structure Prediction of Fatty Acid Binding Site on Human Transmembrane Receptor CD36

2013 ◽  
Vol 7 ◽  
pp. BBI.S12276 ◽  
Author(s):  
Zineb Tarhda ◽  
Oussama Semlali ◽  
Anas Kettani ◽  
Ahmed Moussa ◽  
Nada A. Abumrad ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Binding Site ◽  
Structure Prediction ◽  
Heart Diseases ◽  
3D Structure ◽  
Lipid Binding ◽  
Dimensional Structure ◽  
Target Sequence ◽  
Fatty Acid Binding ◽  
Functional Sites

CD36 is an integral membrane protein which is thought to have a hairpin-like structure with alpha-helices at the C and N terminals projecting through the membrane as well as a larger extracellular loop. This receptor interacts with a number of ligands including oxidized low density lipoprotein and long chain fatty acids (LCFAs). It is also implicated in lipid metabolism and heart diseases. It is therefore important to determine the 3D structure of the CD36 site involved in lipid binding. In this study, we predict the 3D structure of the fatty acid (FA) binding site [127–279 aa] of the CD36 receptor based on homology modeling with X-ray structure of Human Muscle Fatty Acid Binding Protein (PDB code: 1HMT). Qualitative and quantitative analysis of the resulting model suggests that this model was reliable and stable, taking in consideration over 97.8% of the residues in the most favored regions as well as the significant overall quality factor. Protein analysis, which relied on the secondary structure prediction of the target sequence and the comparison of 1HMT and CD36 [127–279 aa] secondary structures, led to the determination of the amino acid sequence consensus. These results also led to the identification of the functional sites on CD36 and revealed the presence of residues which may play a major role during ligand-protein interactions.

Identification of the fatty acid binding site on glutathione S-transferase P

1992 ◽  
Vol 189 (1) ◽  
pp. 197-205 ◽  
Author(s):  
Jun Nishihira ◽  
Teruo Ishibashi ◽  
Masaharu Sakai ◽  
Shinzo Nishi ◽  
Hidemasa Kondo ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Binding Site ◽  
Glutathione S Transferase ◽  
Fatty Acid Binding ◽  
Fatty Acid Binding Site

scholarly journals Characterizing the Fatty Acid Binding Site in the Cavity of Potassium Channel KcsA

Biochemistry ◽  
2012 ◽  
Vol 51 (40) ◽  
pp. 7996-8002 ◽  
Author(s):  
Natalie Smithers ◽  
Juan H. Bolivar ◽  
Anthony G. Lee ◽  
J. Malcolm East
Keyword(s):  
Fatty Acid ◽  
Potassium Channel ◽  
Binding Site ◽  
Fatty Acid Binding ◽  
Potassium Channel Kcsa ◽  
Fatty Acid Binding Site

scholarly journals The Role of Intestinal Fatty Acid Binding Proteins in Protecting Cells from Fatty Acid Induced Impairment of Mitochondrial Dynamics and Apoptosis

2018 ◽  
Vol 51 (4) ◽  
pp. 1658-1678 ◽  
Author(s):  
Suparna Sarkar-Banerjee ◽  
Sourav Chowdhury ◽  
Dwipanjan Sanyal ◽  
Tulika Mitra ◽  
Sib Sankar Roy ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Binding Proteins ◽  
Apoptotic Cell ◽  
Mitochondrial Dynamics ◽  
Ectopic Expression ◽  
Lipid Binding ◽  
Confocal Imaging ◽  
Fatty Acid Binding Proteins ◽  
Mitochondrial Morphology ◽  
Fatty Acid Binding

Background/Aims: The conformation, folding and lipid binding properties of the intestinal fatty acid binding proteins (IFABP) have been extensively investigated. In contrast, the functional aspects of these proteins are not understood and matter of debates. In this study, we aim to address the deleterious effects of FA overload on cellular components, particularly mitochondria; and how IFABP helps in combating this stress by restoring the mitochondrial dynamics. Methods: In the present study the functional aspect of IFABP under conditions of lipid stress was studied by a string of extensive in-cell studies; flow cytometry by fluorescence-activated cell sorting (FACS), confocal imaging, western blotting and quantitative real time PCR. We deployed ectopic expression of IFABP in rescuing cells under the condition of lipid stress. Again in order to unveil the mechanistic insights of functional traits, we arrayed extensive computational approaches by means of studying centrality calculations along with protein-protein association and ligand induced cluster dissociation. While addressing its functional importance, we used FCS and in-silico computational analyses, to show the structural distribution and the underlying mechanism of IFABP’s action. Results: Ectopic expression of IFABP in HeLa cells has been found to rescue mitochondrial morphological dynamics and restore membrane potential, partially preventing apoptotic damage induced by the increased FAs. These findings have been further validated in the functionally relevant intestinal Caco-2 cells, where the native expression of IFABP protects mitochondrial morphology from abrogation induced by FA overload. However, this native level expression is insufficient to protect against apoptotic cell death, which is rescued, at least partially in cells overexpressing IFABP. In addition, shRNA mediated IFABP knockdown in Caco-2 cells compromises mitochondrial dynamics and switches on intrinsic apoptotic pathways under FA-induced metabolic stress. Conclusion: To summarize, the present study implicates functional significance of IFABP in controlling ligand-induced damage in mitochondrial dynamics and apoptosis.

scholarly journals Fat depot origin affects fatty acid handling in cultured rat and human preadipocytes

2001 ◽  
Vol 280 (2) ◽  
pp. E238-E247 ◽  
Author(s):  
Frank Caserta ◽  
Tamara Tchkonia ◽  
Vildan N. Civelek ◽  
Marc Prentki ◽  
Nicholas F. Brown ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Binding Protein ◽  
Lipid Binding ◽  
Fatty Acid Binding Proteins ◽  
Fatty Acid Binding ◽  
Chain Acyl ◽  
Human Preadipocytes ◽  
Fat Depot ◽  
Carnitine Palmitoyltransferase 1 ◽  
Adipose Cells

Regional differences in free fatty acid (FFA) handling contribute to diseases associated with particular fat distributions. As cultured rat preadipocytes became differentiated, FFA transfer into preadipocytes increased and was more rapid in single perirenal than in epididymal cells matched for lipid content. Uptake by human omental preadipocytes was greater than uptake by abdominal subcutaneous preadipocytes. Adipose-specific fatty acid binding protein (aP2) and keratinocyte lipid binding protein abundance was higher in differentiated rat perirenal than in epididymal preadipocytes. This interdepot difference in preadipocyte aP2 expression was reflected in fat tissue in older animals. Carnitine palmitoyltransferase 1 activity increased during differentiation and was higher in perirenal than in epididymal preadipocytes, particularly the muscle isoform. Long-chain acyl-CoA levels were higher in perirenal than in epididymal preadipocytes and isolated fat cells. These data are consistent with interdepot differences in fatty acid flux ensuing from differences in fatty acid binding proteins and enzymes of fat metabolism. Heterogeneity among depots results, in part, from distinct intrinsic characteristics of adipose cells. Different depots are effectively separate miniorgans.

scholarly journals Molecular Cloning, Modeling, and Characterization of Type 2 Metallothionein from Plantago ovata Forsk

Sequencing ◽  
2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Amitava Moulick ◽  
Debashis Mukhopadhyay ◽  
Shonima Talapatra ◽  
Nirmalya Ghoshal ◽  
Sarmistha Sen Raychaudhuri
Keyword(s):  
Molecular Cloning ◽  
Structure Prediction ◽  
3D Structure ◽  
Three Dimensional ◽  
Transcript Level ◽  
Copper Stress ◽  
Dimensional Structure ◽  
Functional Study ◽  
Plantago Ovata

Plantago ovata Forsk is a medicinally important plant. Metallothioneins are cysteine rich proteins involved in the detoxification of heavy metals. Molecular cloning and modeling of MT from P. ovata is not reported yet. The present investigation will describe the isolation, structure prediction, characterization, and expression under copper stress of type 2 metallothionein (MT2) from this species. The gene of the protein comprises three exons and two introns. The deduced protein sequence contains 81 amino acids with a calculated molecular weight of about 8.1 kDa and a theoretical pI value of 4.77. The transcript level of this protein was increased in response to copper stress. Homology modeling was used to construct a three-dimensional structure of P. ovata MT2. The 3D structure model of P. ovata MT2 will provide a significant clue for further structural and functional study of this protein.

scholarly journals The binding of cholesterol and bile salts to recombinant rat liver fatty acid-binding protein

1996 ◽  
Vol 320 (3) ◽  
pp. 729-733 ◽  
Author(s):  
Alfred E. A. THUMSER ◽  
David C. WILTON
Keyword(s):  
Fatty Acid ◽  
Bile Salts ◽  
Fatty Acid Binding Protein ◽  
Binding Protein ◽  
Physiological Role ◽  
Lipid Binding ◽  
Liver Fatty Acid ◽  
Fatty Acid Binding ◽  
Acid Binding Protein ◽  
Wide Range

The physiological role of liver fatty acid-binding protein (L-FABP) has yet to be clarified. An important feature of this member of the family of intracellular lipid-binding proteins is the wide range of compounds that have been identified as potential physiological ligands. By using recombinant L-FABP, the binding of cholesterol, bile salts and their derivatives has been investigated under conditions that allow a direct comparison of the binding affinities of these ligands for fatty acids. The results demonstrate an inability of L-FABP to bind cholesterol, although the anionic derivative, cholesteryl sulphate, will bind under similar assay conditions. Of the bile salts examined, lithocholate and taurolithocholate sulphate showed the greatest binding to L-FABP. It is proposed that an important function of L-FABP is to bind certain physiological amphipathic anions, thus preventing the ‘free’ concentrations of these compounds from exceeding their critical micelle concentration, which could result in cell damage.

scholarly journals RNA 3D structure prediction guided by independent folding of homologous sequences

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Marcin Magnus ◽  
Kalli Kappel ◽  
Rhiju Das ◽  
Janusz M. Bujnicki
Keyword(s):  
Rna Structure ◽  
Structure Prediction ◽  
Tertiary Structure ◽  
3D Structure ◽  
3D Models ◽  
Target Sequence ◽  
Rna Sequences ◽  
Homologous Sequences ◽  
3D Structure Prediction ◽  
Folding Simulations

Abstract Background The understanding of the importance of RNA has dramatically changed over recent years. As in the case of proteins, the function of an RNA molecule is encoded in its tertiary structure, which in turn is determined by the molecule’s sequence. The prediction of tertiary structures of complex RNAs is still a challenging task. Results Using the observation that RNA sequences from the same RNA family fold into conserved structure, we test herein whether parallel modeling of RNA homologs can improve ab initio RNA structure prediction. EvoClustRNA is a multi-step modeling process, in which homologous sequences for the target sequence are selected using the Rfam database. Subsequently, independent folding simulations using Rosetta FARFAR and SimRNA are carried out. The model of the target sequence is selected based on the most common structural arrangement of the common helical fragments. As a test, on two blind RNA-Puzzles challenges, EvoClustRNA predictions ranked as the first of all submissions for the L-glutamine riboswitch and as the second for the ZMP riboswitch. Moreover, through a benchmark of known structures, we discovered several cases in which particular homologs were unusually amenable to structure recovery in folding simulations compared to the single original target sequence. Conclusion This work, for the first time to our knowledge, demonstrates the importance of the selection of the target sequence from an alignment of an RNA family for the success of RNA 3D structure prediction. These observations prompt investigations into a new direction of research for checking 3D structure “foldability” or “predictability” of related RNA sequences to obtain accurate predictions. To support new research in this area, we provide all relevant scripts in a documented and ready-to-use form. By exploring new ideas and identifying limitations of the current RNA 3D structure prediction methods, this work is bringing us closer to the near-native computational RNA 3D models.

scholarly journals Three-dimensional structure of fatty-acid-binding protein from bovine heart

1991 ◽  
Vol 199 (2) ◽  
pp. 271-276 ◽  
Author(s):  
Anke MULLER-FAHRNOW ◽  
Ursula EGNER ◽  
T. Alwyn JONES ◽  
Heinz RUDEL ◽  
Friedrich SPENER ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Binding Protein ◽  
Binding Protein ◽  
Three Dimensional ◽  
Dimensional Structure ◽  
Fatty Acid Binding ◽  
Three Dimensional Structure ◽  
Acid Binding Protein ◽  
Bovine Heart
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