Disease relevance of methanone

• CD8 T cell detection of bacterial infection: sniffing for formyl peptides derived from Mycobacterium tuberculosis [1].
• Freshly made, these cytoplasts respond chemotactically to formyl peptide (fMet-Leu-Phe), and they take up and kill roughly half as many Staphylococcus aureus as their (larger, granular) parent PMN [2].
• Coexpression of the E. coli polypeptide deformylase (DEF), which removes the formyl group from the N-terminal formylmethionine in a polypeptide, rescues the slow-growth phenotype, whereas, coexpression of an inactive mutant of DEF does not [3].
• Binding of formyl peptides to Walker 256 carcinosarcoma cells and the chemotactic response of these cells [4].
• The F-actin induced by formyl-peptide plus GTP was inhibited by pertussis toxin [5].

Psychiatry related information on methanone

• Evidence suggests that beta-amyloid (Abeta) has chemokine-like properties and may act through formyl chemotactic receptors (FPR) to induce pathophysiologically important functional changes in Alzheimer's disease (AD) microglia [6].
• Important factors in achieving success with the HCO are patient compliance and periodic monitoring for refabrication of the orthosis to accommodate skeletal growth, change in foot size or shape, and compression or wear of insert materials [7].
• All HCO programs can be enhanced through online initiatives: wellness and health promotion, risk reduction, prevention, early detection, symptom management, life event management, acute treatment and rehabilitation, disease management and end-of-life improvement [8].

High impact information on methanone

• The formyl group is held by a novel hydrogen bonding network, involving His9 on the bottom of the groove, and the side chain of the P1 methionine is lodged in the B pocket [9].
• The identification of other members of this family, including receptors for the chemokines IL-8 and Mip-1/Rantes, thrombin, formyl peptide, and platelet activating factor, provide new tools for understanding structure-function relationships relevant to the inflammatory process [10].
• Receptors, including those for the Fc end of the immunoglobulin G (ref. 1), the C3b component of complement, formyl peptides and plant lectins have been identified on the surface of neutrophils [11].
• In this study, we isolated formyltransferase (fmt) mutant strains of L. monocytogenes that lacked the ability to add formyl groups to nascent polypeptides [12].
• Tumor necrosis factor alpha, granulocyte colony-stimulating factor, granulocyte/macrophage colony-stimulating factor, and formyl peptide were each found to cause a twofold increase in expression of CD14 on the surface of polymorphonuclear leukocytes (PMN) [13].

Chemical compound and disease context of methanone

• N10-Formyltetrahydrofolate is the formyl donor for glycinamide ribotide transformylase in Escherichia coli [14].
• It is well established that formyl peptide chemoattractants can activate a phospholipase C in leukocytes via a pertussis toxin (PT)-sensitive guanine nucleotide regulatory (G) protein [15].
• These results demonstrate that the NH2-terminal formyl peptides produced by E. coli, of which formyl-methionyl-leucyl-phenylalanine appears to be the major component, are the peptide mediators responsible for leukocyte chemotactic activity in the bacterial culture extracts [16].
• The pool of intracellular formyl peptide receptors localized to the specific granule-enriched fraction appeared functionally coupled to a cosedimenting G-protein in experiments demonstrating modulation of high affinity N-formylmethionylleucyl[3H]phenylalanine binding by guanosine 5'-(3-O-thio)triphosphate or pertussis toxin [17].
• In dibutyryl-cAMP-differentiated HL-60 cells, histamine H1 and formyl peptide receptors mediate increases in the cytosolic Ca2+ concentration ([Ca2+]i) via pertussis toxin-sensitive G proteins of the Gi family [18].

Biological context of methanone

• Thus, it appears that large changes in cytosolic free calcium are not necessary for formyl peptide-induced polymorphonuclear leukocyte chemotaxis [19].
• The binding site comprises C668 and G715 located in a groove accommodating the methionyl side-chain, R700, in the vicinity of the formyl group, Y701 and K702 close to the acyl bond between fMet and tRNA(f)(Met), and the surface lined with residues K702-S660, along which the acceptor arm of the initiator tRNA spans in the direction 3' to 5' [20].
• Binding of both 125I-labeled and tetramethylrhodamine-labeled formyl peptide increases in response to treatment of the culture with polar compounds that induce cell differentiation [21].
• Stimulation of the human neutrophil respiratory burst by formyl peptides is primed by a protein kinase inhibitor, staurosporine [22].
• We investigated signaling pathways downstream of G protein-coupled receptors (GPCRs) that are relevant to alpha4beta1 integrin affinity up-regulation using formyl peptide receptor-transfected U937 cells stimulated with fMLP or stromal-derived factor-1alpha and human peripheral blood monocytes stimulated with multiple chemokines or chemoattractants [23].

Anatomical context of methanone

• Furthermore, the chemotactic activity of purified mitochondrial proteins and disrupted mitochondria was decreased by the formyl peptide antagonist butyloxycarbonyl-phenylalanine-leucine-phenylalanine-leucine-phenylalanine [24].
• We conclude that in the ileum both enzymic degradation and restricted mucosal permeability contribute to the intestinal barrier to luminal bacterial formyl oligopeptides [25].
• Structure-activity studies with various N-formylated peptides suggest the presence of a specific receptor that resembles in specificity the formyl peptide receptor on leukocytes [26].
• Competitive binding experiments using unlabeled formyl peptide analogues indicated that the intracellular binding sites display the same structure-function specificity as formyl peptide receptors on intact polymorphonuclear leukocytes (PMN) or isolated plasma membranes [27].
• Formyl-peptide chemoattractants released from bacteria stimulate G-protein-linked receptors on the surface of neutrophils and regulate the neutrophil cytoskeleton and adhesion apparatus through RhoA-dependent pathways [28].

Associations of methanone with other chemical compounds

• We examined the role of intracellular and extracellular calcium on the ability of human polymorphonuclear leukocytes to migrate chemotactically and reexpress (or recycle) formyl peptide receptors when challenged with the synthetic chemotactic peptide, N-formyl-methionyl-leucyl-phenylalanine (FMLP) [19].
• When either MCT or HCO was fed in the absence of cholesterol, there was little effect on receptor-dependent LDL transport but a 36-43% increase in LDL-cholesterol production [29].
• The PAF receptor antagonist, L-652,731, blocked responses (O2-. production and enzyme release) of rat neutrophils stimulated with PAF but did not block responses triggered by immune complexes, formyl chemotactic peptide or opsonized zymosan particles [30].
• Preincubation of neutrophils with 400 ng/ml component I and 1,600 ng/ml component II of botulinum C2 toxin for 30 min almost completely inhibited the formyl peptide-stimulated polymerization of G-actin and at the same time decreased the amount of F-actin in unstimulated neutrophils by an average of approximately 30% [31].
• The def gene could be inactivated if the fmt gene was also inactivated, or if biosynthesis of N10-formyl-tetrahydrofolate, the formyl donor in methionyl-tRNA(i) transformylation, was blocked by trimethoprim [32].

Gene context of methanone

• Recent studies have proposed a functional link between annexin 1 (ANXA1), an endogenous anti-inflammatory mediator, and receptors of the formyl-peptide family [33].
• These findings prompted us to identify the structural requirement for formyl peptide ligand binding by delineation of the primary structure of the rabbit FPR [34].
• Furthermore, CRAMP induced the chemotaxis of human embryonic kidney 293 cells transfected with either FPRL1 or mouse formyl peptide receptor-2, the mouse homologue of FPRL1, but not by untransfected parental human embryonic kidney 293 cells, confirming the use of FPRL1/mouse formyl peptide receptor-2 by CRAMP [35].
• We conclude that formyl peptide receptors are coupled to three MAPK cascades by Gi proteins [36].
• Human neutrophil Fc gamma RIIIB and formyl peptide receptors are functionally linked during formyl-methionyl-leucyl-phenylalanine-induced chemotaxis [37].

Analytical, diagnostic and therapeutic context of methanone

• Evidence that a formyl-substituted iron porphyrin is the prosthetic group of myeloperoxidase: magnetic circular dichroism similarity of the peroxidase to Spirographis heme-reconstituted myoglobin [38].
• DNA extracted from HCO-treated cells showed no evidence of DNA fragmentation when analyzed by agarose gel electrophoresis [39].
• Neutrophil aggregation in response to formyl peptide was analyzed in blood and isolated cells by fluorescence flow cytometry [40].
• Signal transduction by the formyl peptide receptor. Studies using chimeric receptors and site-directed mutagenesis define a novel domain for interaction with G-proteins [41].
• The low Km (3.64 +/- 0.87 X 10(-7) M) GTPase copurified with the formyl peptide receptor in the plasma membrane fraction obtained by discontinuous sucrose density gradient centrifugation [42].

References