Disease relevance of Cyclization

• Cooperative behavior of Escherichia coli cell-division protein FtsZ assembly involves the preferential cyclization of long single-stranded fibrils [1].
• We recently showed that most DNA molecules extracted from bacteriophage P4 are highly knotted because of the cyclization of the linear DNA molecule confined in the phage capsid [2].
• Stigmatella aurantiaca is shown to produce cycloartenol, the well-known first cyclization product of steroid biosynthesis in plants and algae [3].
• Tetracenomycin (Tcm) F2 cyclase, which catalyzes the cyclization of the anthrone Tcm F2 to the naphthacenone Tcm F1 in the biosynthesis of the anthracycline antibiotic Tcm C in Streptomyces glaucescens, has been purified to homogeneity and characterized [4].
• The structure shows that the reactive electrophile is a 4-methylidene-imidazole-5-one, which is formed autocatalytically by cyclization and dehydration of residues 142-144 with the sequence Ala-Ser-Gly [5].

High impact information on Cyclization

• We now find that certain di- and trinucleotides with free 3' hydroxyl groups reopen the circular IVS at the cyclization junction, producing a linear molecule with the oligonucleotide covalently attached to its 5' end [6].
• According to this model, the guanosine cofactor provides the free 3' hydroxyl necessary to initiate a series of three transfers that results in splicing of the pre-rRNA and cyclization of the excised IVS [7].
• The mechanism and sequence of this cyclase are closely related to those of 2,3-oxidosqualene cyclases that catalyze the cyclization step in cholesterol biosynthesis [8].
• An antibody has been induced that efficiently catalyzes a cationic cyclization in which an acyclic olefinic sulfonate ester substrate is converted almost exclusively (98 percent) to a cyclic alcohol [9].
• An analog of luteinizing hormone-releasing hormone containing a gamma-lactam as a conformational constraint has been prepared with the use of a novel cyclization of a methionine sulfonium salt [10].

Chemical compound and disease context of Cyclization

• Editing function of Escherichia coli cysteinyl-tRNA synthetase: cyclization of cysteine to cysteine thiolactone [11].
• BACKGROUND: The Escherichia coli peptide antibiotic microcin B17 (MccB17) contains thiazole and oxazole heterocycles derived from a distributive yet directional cyclization of cysteines and serines in the McbA precursor catalyzed by MccB17 synthetase [12].
• Isopenicillin N synthase (IPNS) from Streptomyces jumonjinensis (M(r) 37,902) is a non-heme ferrous iron-containing enzyme that catalyzes the oxidative cyclization of the tripeptide delta-(L-alpha-aminoadipoyl)-L-cysteinyl-D-valine (ACV) to form isopenicillin N [13].
• Overall, the data indicate that the loss of the two N-terminal amino acids and the cyclization of glutamate at position 3 do not alter the extracellular toxicity of A beta [14].
• The cyclization domain is responsible for introduction of the thiazoline heterocycle into the growing polyketide/nonribosomal peptide chain from the precursors malonyl-CoA and cysteine through the multiple steps of condensation, cyclization, and dehydration [15].

Biological context of Cyclization

• The lut2 mutations are semidominant, and their biochemical phenotype is consistent with a disruption of epsilon ring cyclization [16].
• We have studied DNA minicircles containing the ATF/CREB binding site for GCN4 by using a combination of cyclization kinetics experiments and Monte Carlo simulations [17].
• Because the components of this gene cluster are required for at least four clearly distinct enzymatic processes (2,3-oxidosqualene cyclization, beta-amyrin oxidation, glycosylation, and acylation), it is unlikely that the cluster has arisen as a consequence of duplication of a common ancestor [18].
• Predicting indirect readout requires knowledge of the variations in DNA curvature and flexibility in the affected region, which we have determined for a series of DNA-binding sites for the E2 regulatory protein by using the cyclization kinetics method [19].
• This unstable intermediate undergoes hydrolysis to form the alpha-ketol or cyclization to give the cyclopentenone [20].

Anatomical context of Cyclization

• Regulation of selectin binding activity by cyclization of sialic acid moiety of carbohydrate ligands on human leukocytes [21].
• The highly purified prostaglandin endoperoxide synthetase from bovine vesicular gland microsomes had two still unresolved enzyme activities; the oxygenative cyclization of 8,11,14-eicosatrienoic acid to produce prostaglandin G1 and the conversion of the 15-hydro-peroxide of prostaglandin G1 to a 15-hydroxyl group, producing prostaglandin H1 [22].
• Synthesis of beauveriolide III (1b), which is an inhibitor of lipid droplet accumulation in macrophages, was achieved by solid-phase assembly of linear depsipeptide using a 2-chlorotrityl linker followed by solution-phase cyclization [23].
• Free nitric oxide (NO) activates soluble guanylate cyclase (sGC), an enzyme, within both pulmonary and vascular smooth muscle. sGC catalyzes the cyclization of guanosine 5'-triphosphate to guanosine 3',5'-cyclic monophosphate (cGMP) [24].
• BM 123, because of its slower cyclization, enters the central nervous system effectively also by the i.p. route [25].

Associations of Cyclization with chemical compounds

• Specifically, chemical synthesis combined with peptide cyclization mediated by nonribosomal thioesterase domains enabled the synthesis of glycosylated cyclopeptides, inhibitors of integrin receptors, peptide/polyketide hybrids, lipopeptide antibiotics, and streptogramin B antibiotics [26].
• In addition to the synthetic potential of these cyclization catalysts, which is the main focus of this review, different enzymes for tailoring of peptide scaffolds as well as the manipulation of carrier proteins with reporter-labeled coenzyme A analogs are discussed [26].
• We propose that the enzyme catalyses the intranuclear cyclization of nicotinamide adenine dinucleotide to cyclic adenosine diphosphate ribose [27].
• We demonstrate a succinimide at the C-terminus of the spliced internal protein, implicating cyclization of asparagine in resolution of the branched intermediate, and we identify an alkali-labile bond in the branched intermediate [28].
• The multifunctional ADP-ribosyl cyclase, CD38, catalyzes the cyclization of NAD(+) to cyclic ADP-ribose (cADPr) [29].

Gene context of Cyclization

• Cyclization of Gln1 to form pyroglutamate (pE) limited the site of cross-linking in the mutant to Lys45, permitting identification of receptor residues that are proximal to this residue of bound EGF [30].
• HMO1 bends DNA, as measured by DNA cyclization assays, facilitating cyclization of 136-, 105-, and 87-bp DNA, but not 75-bp DNA, and it has a significantly longer residence time on DNA minicircles compared with linear duplex DNA [31].
• Cyclization by lactam formation has shown that a core region of human PTH (hPTH) from residues 16-26 binds as an alpha-helix to the receptor and that the biological effects are remarkably sensitive to ring size [32].
• Furthermore, stimulated nuclear extracts depleted of IRF-1 and NF-kappaB cannot induce cyclization [33].
• C-terminal cyclization of an SDF-1 small peptide analogue dramatically increases receptor affinity and activation of the CXCR4 receptor [34].

Analytical, diagnostic and therapeutic context of Cyclization

• Sequence analysis of the intron cyclization junction indicates that the noncoded guanosine and one additional nucleotide are lost from the 5' end of the intron upon cyclization [35].
• They are mechanistically investigated with atomic force microscopy techniques (AFM) on six different faces of 1 when o-phenylenediamine was the reagent (substitution, elimination, cyclization, elimination) and interpreted on the basis of known crystal structure data [36].
• It is concluded that during phototherapy the predominant pathway for the removal of bilirubin from the body in the Gunn rat is by biliary excretion of the geometric photoisomers (EZ)- and (ZE)-bilirubin, derived from Z----E isomerization, and the structural photoisomer (EZ)-cyclobilirubin, formed from intramolecular endo-vinyl cyclization [37].
• Syn- and anti-selective Prins cyclizations of delta,epsilon-unsaturated ketones to 1,3-halohydrins with Lewis acids [38].
• The absolute configurations of the enantiomers of N,N,1-trimethyl-cis- and trans-1-phenyl-1,2,3,4-tetrahydro-3-naphthylamines (Ia and Ib) were assigned tentatively from the circular dichroism spectrum of a bridged ketone derived by cyclization of optically active 1-methyl-cis-1-phenyl-1,2,3,4-tetrahydro-3-naphthoic acid (IIa) [39].

References