Uncategorized

Download e-book Lipoxygenase and lipoxygenase pathway enzymes

Free download. Book file PDF easily for everyone and every device. You can download and read online Lipoxygenase and lipoxygenase pathway enzymes file PDF Book only if you are registered here. And also you can download or read online all Book PDF file that related with Lipoxygenase and lipoxygenase pathway enzymes book. Happy reading Lipoxygenase and lipoxygenase pathway enzymes Bookeveryone. Download file Free Book PDF Lipoxygenase and lipoxygenase pathway enzymes at Complete PDF Library. This Book have some digital formats such us :paperbook, ebook, kindle, epub, fb2 and another formats. Here is The CompletePDF Book Library. It's free to register here to get Book file PDF Lipoxygenase and lipoxygenase pathway enzymes Pocket Guide.

Physico chemical properties were compared to understand the details of the binding sites in all the enzymes and to elucidate important amino acids that can be targeted for drug design. In the same way, comparison of AA binding sites was done pair wise and by multiple alignment in various combinations.

WikiGenes - LOX1 - lipoxygenase 1

It has been identified that aliphatic and aromatic interactions are the most common in all the enzymes. In addition interactions unique to each one of these enzymes were identified. The complete analysis of AA binding sites in the seven enzymes was performed; combinations for the seven enzymes were studied in detail. All the seven enzymes are structurally quite different, yet they share AA as the common binding partner. Comparisons in various combinations showed how they are similar and dissimilar with each other.

Lipoxygenase Inhibitors

This information will be helpful in designing specific as well as common inhibitors. Arachidonic acid AA , the major polyunsaturated fatty acid PUFA present in mammalian systems, is oxygenated by three important pathways — the cyclooxygenase COX , the lipoxygenase LOX and the epoxygenase, to form biologically active molecules such as prostaglandins PGs , leukotrienes LTs , and epoxyeicosatrienoic acids EETs , collectively called as eicosanoids [ 1 ].

It is bifunctional enzyme and exhibits cyclooxygenase and peroxidase activities. It introduces two molecules of oxygen into AA to form PGG 2 , a cyclic hydroperoxy endoperoxide, which is subsequently reduced by peroxidase to give hydroxy endoperoxide, PGH 2 [ 2 ]. COX-1, constitutively expressed in most tissues synthesizes PGs at low levels, and is presumed to function primarily in the maintenance of physiological functions [ 4 - 7 ]. The inducible isoform of COX, COX-2 is induced by several and plays a direct role in inflammation, cancer and various other diseases [ 8 , 9 ].

COX-3, a product of COX-1 gene has been identified as the alternatively spliced form found mostly in the brain. The other important group of enzymes involved in AA metabolism, LOXs, are closely related non-heme iron containing dioxygenases which catalyze the addition of molecular oxygen to form hydroperoxy metabolites HPETEs. LOXs are broadly classified as 5-, 12, and LOXs in animals [ 10 , 11 ] based on regio and stereo specific incorporation of molecular oxygen on AA.

Cox lox pathway (arachnoid acid metabolites)【Drugofchoice】

Eicosanoids generated by these LOXs in a tissue specific manner play key role in various diseases. In various LOX isoforms the active sites have modifications to effect specific reactions but the basic enzyme structures are conserved [ 13 - 16 ]. Non steroidal anti-inflammatory drugs NSAIDs are the most commonly used remedies for arthritis and some inflammation associated diseases. These COXIBs, however were shown to have cardiac side effects when used at high concentrations for a long period. Development of specific inhibitors or dual inhibitors of enzymes involved in AA metabolism is of great challenge.

The main objective of this study is to compare binding site features in AA metabolizing enzymes and to elucidate important amino acids that can be targeted for drug design. In this study five isoforms of LOX and two isoforms of COX enzymes to generate reliable data enzymes having crystal data alone were considered collectively were considered for the analysis. Structural aspects of these enzymes were understood using receptor based pharmacophore models and by comparison of physicochemical properties at binding site were performed.

Multitarget drug design is gaining prominence in modern drug discovery and in silico approaches may play a very crucial role in such approaches [ 19 ]. In this context this study will aid development of more potential inhibitors of AA metabolizing enzymes. The hydrophobic nature of AA substrate suggests that predominantly hydrophobic residues line the substrate-binding pocket.

The binding sites were initially compared in a pair wise manner. Pair wise surface alignments of the enzymes detect more common features and help in the elucidation of important amino acid similarities between members of same class and also individually with enzymes of another family.

As mentioned earlier, COX-1 and COX-2 are members of the same family and they share large similarity with each other in their enzyme reaction with their common substrate AA. Pairwise alignments of the binding sites in MultiBind showed that they have great similarity at the AA binding site.

They were scored Apart from these, common hydrogen bond donor DON , hydrogen bond acceptor ACC and mixed hydrogen bond donor and acceptor e. The common physico-chemical properties and the contributing amino acids are shown in Additional file 1 : Table S1. Despite the relatively safe pharmacological profile of the COXIBs like celecoxib and valdecoxib there is concern regarding their use in patients with emerging news of myocardial infarction on prolonged use.

The patterns or important interactions observed will further aid in planning drug design experiments.

Though the hydrogen bond forming functional groups are not of the same amino acids, they can be helpful in the design of common inhibitors. Glycine possesses same property in both enzymes. The amino acids contributing for the same physicochemical properties are shown in Additional file 1. They are aligned with scores The binding site of 5-LOX and LOX have five ALI features in common out of the ten common physicochemical properties identified, indicating it to be the most prominent property in the binding site.

Two PII interactions are also observed. Both of them act as ACC. The other prominent amino acid differences are shown in Additional file 1. The LOX was scored The high score of LOX with 5-LOX is because of the presence of seven identical amino acids contributing for common interacting groups. The binding site of COX-1 was compared with that of the LOXs to recognise the structurally conserved physicochemical patterns. Multiple alignment of 3—7 binding sites were performed.


  • Lipoxygenase!
  • Kant and the Subject of Critique: On the Regulative Role of the Psychological Idea.
  • Arachidonate 5-lipoxygenase - Wikipedia?
  • Fischers Fury;
  • Developments in Strategic and Public Management: Studies in the US and Europe.

The physicochemical similarities observed in various combinations are included in Additional file 1 and some of the alignments are discussed below:. It has been observed that the number of features range from 6— Alignment of the five binding sites of COXs and animal LOXs indicated a common pattern of five physicochemical properties. ALI interactions are more in number in this multiple alignment. The score obtained when aligned was The receptor models generated showed that the amino acids of both the proteins 5-LOX and COX-2 have common interacting groups at the active site.


  • Lipoxygenases and their metabolites in formation of plant stress tolerance.
  • Login using.
  • Technical English 4 Course Book.
  • Conjugated Polymers: The Novel Science and Technology of Highly Conducting and Nonlinear Optically Active Materials;
  • Introductory Chemistry: An Active Learning Approach;
  • Editing Wikipedia articles;
  • The Condition of English: Literary Studies in a Changing Culture (Contributions to the Study of Education)!

Docking results supplemented the models. The dimethylcyclopentane moiety formed hydrophobic interactions with few common ALI features observed. Hence, the docking results showed that the model generated can be used to elucidate the common features and can be further used in the design of dual inhibitors. This site point can be further used for lead optimization employing site point connection method.

Hence, it can be mentioned that a functional group which interacts with amide group of 5-LOX and repels with carboxylic group in LOX can be used to develop specific 5-LOX inhibitor.

Linoleate 13S-lipoxygenase 3-1, chloroplastic

The hydroxyl group of hydroxyurea formed strong hydrogen bond with the amide group of Gln In LOX, the inhibitor did not bind at the binding site this may be due to repulsion between carboxyl group of Glu and the inhibitor. The goal of drug discovery is to design exquisitely selective ligands that act on a single disease target. The current approach is that safer, more effective drugs will result from designing very selective ligands where undesirable and potential side effects have been removed [ 19 ].

Multitarget strategies have also gained importance in the recent time.

Background

To design a specific or multitarget inhibitor it is very important to know the binding site patterns in closely related pathways. In a recent study, Doble et al. In the present study we aimed to understand the physicochemical features unique or similar in AA metabolizing enzymes. Previous studies suggested that this small change in amino acid provides additional space in COX-2 binding pocket. Chemical Reviews. Current Opinion in Lipidology. Cell Biology International. European Journal of Pharmacology. WikiGenes - Collaborative Publishing. Retrieved 17 April Bibcode : Sci Journal of the American Chemical Society.

Carrier proteins , metalloproteins : iron-binding proteins. Ferritin Bacterioferritin Lactoferrin Transferrin. Hemerythrin Inositol oxygenase Iron-sulfur protein Lipoxygenase Tyrosine hydroxylase. Oxidoreductases : monooxygenases EC 1. Firefly luciferase.


  • PHP for Absolute Beginners (2nd Edition);
  • Inhibitors of the 5-Lipoxygenase Pathway in Atherosclerosis.
  • Lipoxygenases and their metabolites in formation of plant stress tolerance!
  • The Tibetan Buddhism Reader!
  • Lipoxygenase as a versatile biocatalyst.

Inositol oxygenase. Allosteric regulation Cooperativity Enzyme inhibitor Enzyme activator. EC number Enzyme superfamily Enzyme family List of enzymes. Biology portal. Categories : EC 1.