Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: DrugBank:EXPT02079 (lysine)
 58,762 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cytochrome c is modified by covalent binding of pyridoxal phosphate (PLP) to lysine residues. One di-substituted [(PLP)2--C] and two mono-substituted derivatives [(PLP)--c and (PLP)''--c] were obtained and precisely purified. The peak at 695 nm and CD-spectra in 190--600 nm region show that all derivatives have native conformation. The differential UV-spectra of the derivatives against native protein show that in (PLP)2--c there is a contact dipole-dipole interaction between PLP chromophores. It is calculated that the N-atoms of the two PLP-substituted lysines must be at a distance less than or equal to 12 A. Analysing our and literature data, one may suppose that Lys-13 and Lys-87 are the most probable candidates for modification with PLP. (PLP)---c and (PLP)''--c behave differently during ion-exchange chromatography and when added to cytochrom c-depleted mitochondria. (PLP)''--c restores electron transfer at higher concentrations than (PLP)'--c. Both they restore fully succinate and ascorbate oxidation but at considerably higher concentrations than the native protein, i. e. modification of any one of the reactive towards PLP lysines descreases but does not exclude the interaction with its reductase and oxidase. The effective equilibrium constants of binding of modified derivatives to cytochrome c-depleted mitochondria are lower than the constant for native protein. Together with decrease in binding activity, Hill coefficients increase. From our results it may be supposed that probably the binding sites of cytochrome c for its reductase and oxidase partially overlap.
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PMID:[Pyridoxalphosphate-modified derivatives of cytochrome c. Mono- and disubstituted derivatives: characteristics and effect on electron transport in cytochrome c-depleted mitochondria]. 624 46

Pyridoxal phosphate photoinactivates the peptidyltransferase activity of 50-S ribosomal subunits, LiCl split proteins and protein L16. Ethyromycin exhibits significant protection. These results, taken together with earlier reports, indicate the involvement of the single histidine of L16 in peptidyltransferase activity. The adjacent association in L16 of histidine and lysine indicates that pyridoxal phosphate should represent a selective inhibitor of peptidyltransferase activity.
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PMID:The modification of the peptidyltransferase activity of 50-S ribosomal subunits, LiCl-split proteins and L16 ribosomal protein by pyridoxal phosphate. 625 59

The preparation, purification and characterization of the three singly, three doubly and one triply substituted derivatives of cytochrome c modified by pyridoxal phosphate (PLP) at lysine residues are reported. The PLP positions in PLP derivatives were determined by the amino acid analysis and sequence of PLP peptides. The results identified the lysine at position 86 in one of the singly substituted, lysine 79 in the other singly substituted and lysines 86 and 79 in the third doubly substituted cytochrome c derivatives. The area surrounding phenylalanine 82 forms the predominant PLP binding site on the cytochrome c molecule. The visible, CD and proton NMR spectra, the full intensity of the conformation-sensitive 695 nm band and the oxidation-reduction properties provide evidence to confirm the conclusion that singly and doubly substituted PLP cytochromes c retain the native conformation. The ability to restore both succinate and ascorbate/TMPD oxidation in cytochrome c-depleted mitochondria decreases in the order: native cytochrome c greater than PLP-Lys-79-cytochrome c greater than PLP-Lys-86-cytochrome c greater than PLP-Lys-79,86-cytochrome c greater than triply substituted derivative.
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PMID:Pyridoxal phosphate modified cytochromes c. Identification and electron transfer properties. 632 73

The rate of quenching of the fluorescence of pyridoxal 5'-phosphate in the active site of the beta 2 subunit of tryptophan synthase from Escherichia coli was measured to estimate the accessibility of the coenzyme to the small molecules iodide and acrylamide. The alpha subunit and the substrate L-serine substantially reduced the quenching rate. For iodide, the order of decreasing quenching was: Schiff's base of N alpha-acetyl-lysine with pyridoxal 5'-phosphate greater than holo beta 2 subunit greater than holo alpha 2 beta 2 complex approximately equal to holo beta 2 subunit + L-serine greater than holo alpha 2 beta 2 complex + L-serine. The coenzyme in the beta 2 subunit is apparently freely accessible to both iodide and acrylamide (kappa approximately equal to 2 X 10(9) M-1 s-1), but the alpha subunit and L-serine decrease the rate by factors of 2-5. Quenching of the fluorescence of the single tryptophan residue of the beta 2 subunit revealed that the apo and holo forms exist in different states, whereas the alpha subunit stabilizes a third conformation. As the alpha subunit binds to the beta 2 subunit, the tryptophan residue, which is within 2.2 nm of the active site of the beta 2 subunit, probably rotates with respect to the plane of the ring of the coenzyme, such that fluorescence energy transfer from tryptophan to pyridoxal phosphate is greatly reduced. The alpha subunit strongly protects the active-site ligand indole propanol phosphate from quenching with acrylamide, consistent with the active site being deep in a cleft in the protein. Iodide induces dissociation of the holo alpha 2 beta 2 complex [E. W. Miles & M. Moriguchi (1977) J. Biol. Chem. 252, 6594-6599]. The effect of iodide on the fluorescence properties of holo alpha 2 beta 2 complex allows us to estimate an upper limit for the dissociation constant for the alpha 2 beta 2 complex of 10(-8) M, in the absence of iodide.
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PMID:The accessibility of the active site and conformation states of the beta 2 subunit of tryptophan synthase studied by fluorescence quenching. 634 54

The effect of chemical modification on the acetylcholinesterase and the aryl acylamidase activities of purified acetylcholinesterase from electric eel and basal ganglia was investigated in the presence and absence of acetylcholine, the substrate of acetylcholinesterase, and 1,5-bis[4-(allyldimethylammonium)phenyl]pentan-3-one dibromide (BW284C51), a reversible competitive inhibitor of acetylcholinesterase. Trinitrobenzenesulfonic acid, pyridoxal phosphate, acetic anhydride, diethyl pyrocarbonate, and 2-hydroxy-5-nitrobenzyl bromide under specified conditions inactivated both acetylcholinesterase and aryl acylamidase in the absence of acetylcholine and BW284C51. Chemical modifications in the presence of acetylcholine and BW284C51 by all the above except diethyl pyrocarbonate selectively prevented the loss of acetylcholinesterase but not aryl acylamidase activity; modification by diethyl pyrocarbonate in the presence of acetylcholine and BW284C51 prevented the loss of both acetylcholinesterase and aryl acylamidase activities. Treatment with N-acetylimidazole resulted in the inactivation of acetylcholinesterase and the activation of aryl acylamidase. These changes in both the activities could be prevented by acetylcholine and BW284C51. Modification by phenylglyoxal, 2,4-pentanedione, or N-ethylmaleimide did not affect the enzyme activities. Indophenylacetate hydrolase activity followed a pattern similar to that of acetylcholinesterase in all the above modification studies. The results suggested essential lysine, tyrosine, tryptophan, and histidine residues for the active center of acetylcholinesterase and essential lysine, histidine, and tryptophan residues for the active center of aryl acylamidase.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Chemical modification of acetylcholinesterase from eel and basal ganglia: effect on the acetylcholinesterase and aryl acylamidase activities. 638 42

Storage of milk powder under unfavourable conditions accelerates the normally slow deterioration in nutritional quality. The effects of such storage on the water-soluble vitamin composition were examined. (a) Spray-dried whole milk containing 25 g water/kg was stored at 60 degrees and 70 degrees and sampled weekly to 9 weeks. (b) Spray-dried whole milk and skimmed milk were adjusted to contain 40 and 100 g water/kg and stored at 37 degrees in nitrogen and in oxygen. Samples were taken for analysis at intervals during storage. The samples were analysed for eight B-complex vitamins and ascorbic acid, and also for total lysine, 'reactive lysine' and 'lysine as lactulosyl-lysine'. Storage at 60 degrees caused rapid destruction of folic acid (53% loss at 4 weeks) and slower loss of thiamin, vitamin B6 and pantothenic acid (18% at 8 weeks). There was no change in the content of riboflavin, biotin, nicotinic acid and vitamin B12. At 70 degrees the rate of destruction of the four labile vitamins was much increased; 18% or less survived at 4 weeks. At 37 degrees and 40 g water/kg there was little change in total and 'reactive' lysine during storage for 57 d. Lactulosyl-lysine was demonstrably present but at low concentration. There was considerable loss of folate (72%) and ascorbate (91%) during storage for 30 d in O2, but no significant loss in N2. Thiamin fell by approximately 12% in 57 d, equally in O2 and N2. The content of the remaining vitamins was unchanged. At 100 g water/kg there were progressive Maillard changes. During 27 d in N2 the colour changed from cream to pale brown, but in O2 there was no perceptible colour change. Total lysine fell by 20% in 27 d, and 'reactive lysine' by 30%. Folate was stable during 16 d in N2, but largely (94%) destroyed in O2. Ascorbic acid was also destroyed in N2 as in O2. Thiamin fell by 41% in 27 d, equally in O2 and N2. Vitamin B6 was more labile, especially in N2, falling by 71% in 16 d. With skimmed-milk powder containing 100 g water/kg, storage at 37 degrees in O2 and N2 gave much the same results as for the corresponding whole-milk powder. The presence of milk fat had no marked effect on the stability of the water-soluble vitamins. Destruction of vitamins was clearly linked to the progress of Maillard-type reactions and was strongly influenced by time and temperature of storage, moisture content and, in some instances, by the presence of O2.
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PMID:Storage of milk powders under adverse conditions. 2. Influence on the content of water-soluble vitamins. 640 21

Inactivation of formate dehydrogenase by formaldehyde, pyridoxal and pyridoxal phosphate was studied. The effects of concentrations of the modifying agents, substrates, products and inhibitors on the extent of the enzyme inactivation were examined. A complete formate dehydrogenase inactivation by pyridoxal, pyridoxal, phosphate and formaldehyde is achieved by the blocking of 2, 5 and 13 lysine residues per enzyme subunit, respectively. The coenzymes do not protect formate dehydrogenase against inactivation. In the case of modification by pyridoxal and pyridoxal phosphate a complete maintenance of the enzyme activity and specific protection of one lysine residue per enzyme subunit is observed during formation of a binary formate-enzyme complex, or a ternary enzyme--NAD--azide complex. One lysine residue is supposed to be located at the formate-binding site of the formate dehydrogenase active center.
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PMID:[Chemical modification of the lysine residues of bacterial formate dehydrogenase]. 640 66

Inactivation of the beta 2 subunit and of the alpha 2 beta 2 complex of tryptophan synthase of Escherichia coli by the arginine-specific dicarbonyl reagent phenylglyoxal results from modification of one arginyl residue per beta monomer. The substrate L-serine protects the holo beta 2 subunit and the holo alpha 2 beta 2 complex from both inactivation and arginine modification but has no effect on the inactivation or modification of the apo forms of the enzyme. This result and the finding that phenylglyoxal competes with L-serine in reactions catalyzed by both the holo beta 2 subunit and the holo alpha 2 beta 2 complex indicate that L-serine and phenylglyoxal both bind to the same essential arginyl residue in the holo beta 2 subunit. The apo beta 2 subunit is protected from phenylglyoxal inactivation much more effectively by phosphopyridoxyl-L-serine than by either pyridoxal phosphate or pyridoxine phosphate, both of which lack the L-serine moiety. The phenylglyoxal-modified apo beta 2 subunit binds pyridoxal phosphate and the alpha subunit but cannot bind L-serine or L-tryptophan. We conclude that the alpha-carboxyl group of L-serine and not the phosphate of pyridoxal phosphate binds to the essential arginyl residue in the beta 2 subunit. The specific arginyl residue in the beta 2 subunit which is protected by L-serine from modification by phenyl[2-14C]glyoxal has been identified as arginine-148 by isolating a labeled cyanogen bromide fragment (residues 135-149) and by digesting this fragment with pepsin to yield the labeled dipeptide arginine-methionine (residues 148-149). The primary sequence near arginine-148 contains three other basic residues (lysine-137, arginine-141, and arginine-150) which may facilitate anion binding and increase the reactivity of arginine-148. The conservation of the arginine residues 141, 148, and 150 in the sequences of tryptophan synthase from E. coli, Salmonella typhimurium, and yeast supports a functional role for these three residues in anion binding. The location and role of the active-site arginyl residues in the beta 2 subunit and in two other enzymes which contain pyridoxal phosphate, aspartate aminotransferase and glycogen phosphorylase, are compared.
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PMID:L-serine binds to arginine-148 of the beta 2 subunit of Escherichia coli tryptophan synthase. 641 46

Treatment of yeast fatty acid synthetase with pyridoxal 5'-phosphate inhibited the enzyme. Assays of the partial activities of the pyridoxal phosphate-treated synthetase showed that only the beta-ketoacyl reductase was significantly inhibited. NADPH prevented inactivation of the enzyme by pyridoxal phosphate, indicating that pyridoxal modifies a residue near or in the beta-ketoacyl reductase site. The pyridoxal-treated synthetase shows a fluorescence spectrum with a maximum of 426 nm after uv irradiation at 325 nm. Binding of the pyridoxal phosphate to the synthetase is reversible as shown by the disappearance of the fluorescence band after dialysis of pyridoxal-treated enzyme. Reduction with NaBH4 of the pyridoxal-treated enzyme eliminates this fluorescence maximum and causes the appearance of a new band at 393 nm. These observations suggest that pyridoxal phosphate interacts with the synthetase by forming a Schiff base with lysine residue at the beta-ketoacyl reductase site. Amino acid analyses of the HCl hydrolysates of the borohydride-reduced, pyridoxal-treated synthetase showed the presence of 6 mol of N6-pyridoxal derivative of lysine per mole of fatty acid synthetase, indicating the presence of six sites of beta-ketoacyl reductase in the native enzyme. Autoradiography of sodium dodecyl sulfate-polyacrylamide gels of the pyridoxal phosphate enzyme reduced with NaB3H4 indicates that the alpha subunit contains the beta-ketoacyl reductase domain. These findings are consistent with the proposed structure of the alpha 6 beta 6 complex required for palmitoyl-CoA synthesis.
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PMID:Inactivation of yeast fatty acid synthetase by modifying the beta-ketoacyl reductase active lysine residue with pyridoxal 5'-phosphate. 641 72

Glyceraldehyde-3-phosphate dehydrogenase (EC 1.2.1.12) binds reversibly to human erythrocyte membranes. Several specific amino acid residues involved in the enzyme-membrane contact region have already been identified. These include tyrosine 46 and threonine 150. Covalent modification of lysines 212 and 191 with pyridoxal phosphate results in a decreased affinity of the enzyme for erythrocyte membranes if the enzyme-linked pyridoxal phosphate is not reduced prior to binding. Reduction of the pyridoxal phosphate-lysine complex completely inhibits the binding of the enzyme to erythrocyte membranes. These results suggest a role for lysines 212 and 191 in the interaction of glyceraldehyde-3-phosphate with human erythrocyte membranes.
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PMID:Role of lysine residues in the binding of glyceraldehyde-3-phosphate dehydrogenase to human erythrocyte membranes. 641 59


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