Disease relevance of DICYCLOHEXYLCARBODIIMIDE

• DCCD inhibits protein translocation into plasma membrane vesicles from Escherichia coli at two different steps [1].
• HeLa S3 cells were protected against infection by poliovirus type I by the presence of monensin and N,N'-dicyclohexylcarbodiimide (DCCD), compounds elevating the pH of acidic intracellular compartments [2].
• Restoration of oxidative phosphorylation by purified N,N'-dicyclohexylcarbodiimide-sensitive latent adenosinetriphosphatase from Mycobacterium phlei [3].
• Specific protection by Na+ or Li+ of the F1F0-ATPase of Propionigenium modestum from the reaction with dicyclohexylcarbodiimide [4].
• Calcium uptake in the presenceof ATP is blocked by dicyclohexylcarbodiimide, ADP, p-chloromercuriphenylsulfonate, by the proton-conducting ionophores m-chlorophenylcarbonylcyanide hydrazone, nigericin, monensin, and gramicidin D, but not by potassium cyanide, anoxia, or valinomycin (in the presence of potassium) [5].

High impact information on DICYCLOHEXYLCARBODIIMIDE

• The ATP synthase with a Na+-permeable stator catalyzed 22Na+out/Na+in-exchange after reconstitution into proteoliposomes, which was not significantly affected by DCCD modification of the c subunit oligomer, but was abolished by the additional presence of ATP or by a membrane potential (DeltaPsi) of 90 mV [6].
• Endosomal insulin degradation was inhibited markedly in the presence of pH dissipating agents such as nigericin, monensin, and chloroquine or the proton translocase inhibitors N-ethylmaleimide (NEM) and dicyclohexylcarbodiimide (DCCD) [7].
• Membranes devoid of F1 did show, however, residual translocation activity that was also found to be inhibitable by DCCD [1].
• 8. The pH could be raised by the lysosomotropic agent ammonium chloride, the protonophore carbonyl cyanide p-trifluoromethoxyphenyl-hydrazone (CCCP) and the ATPase inhibitors dicyclohexylcarbodiimide (DCCD) and sodium vanadate [8].
• In vitro translocation of periplasmic and outer membrane proteins into inverted plasma membrane vesicles from Escherichia coli was completely prevented by the H+-ATPase inhibitor N,N'-dicyclohexylcarbodiimide (DCCD) [1].

Chemical compound and disease context of DICYCLOHEXYLCARBODIIMIDE

• Binding of methomyl or T-toxin decreases DCCD cross-linking of URF13 oligomers expressed in either E. coli or cms-T mitochondria [9].
• Pyridine nucleotide transhydrogenase (EC 1.6.1.1) from Escherichia coli was investigated with respect to the role of glutamic and aspartic acid residues reactive to N,N'-dicyclohexylcarbodiimide (DCCD) and potentially involved in the proton-pumping mechanism of the enzyme [10].
• The inhibition of the membrane-bound adenosine triphosphatase of Escherichia coli by DCCD (dicyclohexylcarbodi-imide) is studied under conditions of varying KCl concentration [11].
• Where the NADH-quinone reductase segment involved an energy-coupling site (e.g., in bovine heart and rat liver mitochondria, and in Paracoccus denitrificans, Escherichia coli, and Thermus thermophilus HB-8 membranes), DCCD acted as an inhibitor of ubiquinone reduction by NADH [12].
• Proton-pumping N,N'-dicyclohexylcarbodiimide-sensitive inorganic pyrophosphate synthase from Rhodospirillum rubrum: purification, characterization, and reconstitution [13].

Biological context of DICYCLOHEXYLCARBODIIMIDE

• Substitutional mutations at this DCCD binding site also eliminate toxin sensitivity [14].
• 2. The ATPase inhibitor, dicyclohexylcarbodiimide (DCCD), prevented NTP hydrolysis and inhibited delta pH formation [15].
• It is proposed that dicyclohexylcarbodiimide and oligomycin inhibit ATPase activity by causing a conformational change in the F0 portion of the complex that is transmitted to F1, resulting in an impaired binding of substrate in catalytic sites [16].
• Symport of D-glucose/H+ and L-proline/H+ was measured directly in cells pretreated with KCN and DCCD [17].
• By analogy, it is proposed that modifications (e.g., protonation/deprotonation) of the DCCD-binding protein effected by protonic energy alter the conformation of F1 and bring about the substrate/product binding changes that appear to be essential features of the mechanism and regulation of oxidative phosphorylation [18].

Anatomical context of DICYCLOHEXYLCARBODIIMIDE

• N,N'-dicyclohexylcarbodiimide cross-linking suggests a central core of helices II in oligomers of URF13, the pore-forming T-toxin receptor of cms-T maize mitochondria [9].
• As the proteolipids of sarcoplasmic reticulum bind dicyclohexylcarbodiimide under conditions in which Ca2+ release is blocked and as they have previously been shown to have Ca2+ ionophoric activity, we propose that the Ca2+-release channel either resides in the proteolipids or is controlled by H+ fluxes through the proteolipids [19].
• Treatment of submitochondrial particles with dicyclohexylcarbodiimide or oligomycin so as to cause about 90% inhibition of ATPase activity was accompanied by a decrease in the binding of [gamma-32P]ATP in high-affinity catalytic sites [16].
• We have cloned and sequenced the gene encoding the DCCD-binding protein (proteolipid) of the H+-ATPase of bovine chromaffin granules [20].
• Interactions of dicyclohexylcarbodiimide with myelin proteolipid [21].

Associations of DICYCLOHEXYLCARBODIIMIDE with other chemical compounds

• When cells with surface-bound virus were exposed to low pH, the virus entered efficiently, even in the presence of monensin and DCCD [22].
• H+ transport by coated vesicles was not inhibited by vanadate (0.1 mM) or ouabain (2 mM) and differed from H+ transport by rat liver submitochondrial particles in its greater resistance to inhibition by oligomycin (10 pM to 10 microM) and N,N'-dicyclohexylcarbodiimide (DCCD) (0.1-100 microM) and its sensitivity to N-ethylmaleimide (0.1-2 mM) [23].
• Kinetics of inhibition for ethinyl estradiol and propylene glycol endosomes were similar for the proton pump inhibitors N-ethylmaleimide (50% inhibitory concentrations of 13.5 and 18.1 mumol/L), dicyclohexylcarbodiimide (50% inhibitory concentrations of 206 and 216 mumol/L) and bafilomycin A (50% inhibitory concentrations of 11 and 6 nmol/L) [24].
• Glutamate 72 in VDAC1, shown previously to bind dicyclohexylcarbodiimide (DCCD), which inhibits hexokinase isoform I (HK-I) binding to mitochondria, was mutated to glutamine [25].
• The inhibitors dicyclohexylcarbodiimide and N-ethylmaleimide (in alpha S373C/beta Y331W mutant F1) gave potent inhibition of multisite ATPase activity without significantly affecting MgATP binding stoichiometry or cooperativity [26].

Gene context of DICYCLOHEXYLCARBODIIMIDE

• Binding of HK-I to mitochondria expressing E72Q-mVDAC1, as compared to native VDAC1, was decreased by approximately 70% and rendered insensitive to DCCD [25].
• Functional role of aspartyl and glutamyl residues in the membrane segments of the yeast PMA1 ATPase: interaction with DCCD [27].
• The preferential binding of dicyclohexylcarbodiimide to cytochrome b and phospholipids in soluble complex III from yeast mitochondria [28].
• Although independent of Mdl1 activity, complex formation is impaired upon inhibition of the F(1)F(0)-ATP synthase with oligomycin or N,N'-dicyclohexylcarbodiimide [29].
• This finding rules out the possibility that contaminating F0 ATPase gives rise to the DCCD binding exhibited by PLP and confirms the possibility that PLP has proton channel activity, as suggested by Lin and Lees (1,2) [30].

Analytical, diagnostic and therapeutic context of DICYCLOHEXYLCARBODIIMIDE

• Western blot analysis showed that the [14C] DCCD-labeled 82-kDa protein is not a DCCD-crosslinked product [31].
• Titration of the reconstituted membrane vesicles with dicyclohexylcarbodiimide revealed a similar sensitivity of the homologous and hybrid F1F0 complexes towards the inhibitor [32].
• In the "high performance liquid chromatography (HPLC) peak area" method, the DCCD-modified subunit c was separated from unmodified subunit c on an anion exchange AX300 HPLC column, and the areas of the peaks from the chromatogram quantitated [33].
• Two major polypeptides, 72 and 60 kDa, that copurified with the ATPase activity and the 14-18-kDa DCCD-binding peptide are postulated to be subunits of a holoenzyme of 300-600 kDa (estimated by gel filtration) [34].
• The denatured 82-kDa protein, identified by its selective labeling with [14C]dicyclohexylcarbodiimide (DCCD), was purified by preparative two-dimensional gel electrophoresis [31].

References