2,6-Diamino-4-hexynoic acid, a lysine analog

Davis, Alvie L.; Lloyd, R. A.; Maul, Stephen B.; Cook, Drusilla E.; McCord, Tommy J.

doi:10.1016/s0003-9861(64)80009-6

Cited by 8 publications

(5 citation statements)

References 5 publications

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“…The distribution of L-lysine e-transaminase in procaryotes (or eucaryotes) has not been reported, and it is unclear if this enzyme is the in vivo target for these lysine analogues (Jansen & Kerling, 1970;Davis et al, 1964). Few other enzymes process lysine at carbon 6.…”

Section: Discussionmentioning

confidence: 99%

“…Similarly, írans-4-lysene was prepared from trans-2-butene 1,4-dichloride (Eastman) after fractional distillation. Both cis-and rmns-4-lysene had been prepared previously by Davis et al (1964).…”

Section: Methodsmentioning

confidence: 99%

“…In fact, a homogeneous L-lysine e-transaminase from Achromobacter liquidum (Soda & Misono, 1968 does undergo time-dependent inactivation during processing of these lysine analogues, while a partially purified pseudomonad lysine -racemase (Yorifugi et al, 1971) shows no inactivation during -hydrogen exchange. These three lysine analogues have been prepared previously and tested as bacterial growth inhibitors, but no molecular interpretations were offered for their modes of action (Jansen et al, 1979;Davis et al, 1964).…”

Section: Camille and Henry Dreyfusmentioning

confidence: 99%

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Studies with mechanism-based inactivators of lysine .epsilon.-transaminase from Achromobacter liquidum

Shannon¹,

Coppersmith²,

Walsh³

1979

Biochemistry

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Analogues of lysine containing a 4,5-acetylenic linkage (lysyne) or a cis- or trans-4,5-olefinic linkage (lysenes) function as substrates for a homogeneous L-lysine epsilon-transaminase from Achromobacter liquidum but partition between transamination and time-dependent inactivation. The partition ratio is lowest for lysyne (40 per inactivation event) and higher for trans-lysene (160 per inactivation event), and the cis-lysene transaminates 1600 times per inactivation event. cis-Lysene yields alpha-picolinate as a detectable accumulating product, presumably from cyclization of initial 6-aldehyde to dihydropicolinate and spontaneous autoxidation. The trans isomer also yields some picolinate as an identifiable product. The product from the few lysyne turnovers is as yet unknown but has strong absorbance at 318 nm. The inactive enzyme species from all three lysine analogues slowly (overnight) regain full activity after gel filtration chromatography and dialysis, suggesting reversal of the initial adduct-forming reaction. Initial studies with partially purified pseudomonad lysine alpha-racemase show alpha-3H incorporation from 3H2O but no inactivation consistent with the expectation that these lysine analogues could act readily as mechanism-based inactivators for pyridoxal P enzymes which act at the epsilon- but not the alpha-carbon of lysine.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Camille and Henry Dreyfusmentioning

confidence: 99%

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Studies with mechanism-based inactivators of lysine .epsilon.-transaminase from Achromobacter liquidum

Shannon¹,

Coppersmith²,

Walsh³

1979

Biochemistry

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“…Another result of these studies has revealed that several lysine analogues replace lysine as hydroxylysine does (5,6,15), i.e., by preventing lysine-depletion lysis despite their growth-inhibitory action. In all lactic acid bacteria tested, the inhibition indices ranged from 3 to 30.…”

Section: L-lysine Inhibits the Condensation Of Asparticmentioning

confidence: 99%

Effect of Hydroxylysine on the Biosynthesis of Lysine in Streptococcus faecalis

1968

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We were able to show that two lysine-independent mutants of Streptococcus faecalis ATCC 8043 contained the enzymes for the usual bacterial pathway for lysine biosynthesis. Because of this synthetic capacity, one mutant, the Lys+OHLyss strain, could not grow in the presence of hydroxylysine without a lysine supplement. Both lysine and hydroxylysine inhibited the first enzyme of the pathway, aspartokinase. Unlike the Escherichia coli enzyme, S.faecalis dihydrodipicolinic acid synthetase was not inhibited by either lysine or hydroxylysine. Both amino acids caused the repression of dihydrodipicolinic acid synthetase and diaminopimelic acid decarboxylase. Failure of Lys+OHLyss strain to grow in hydroxylysine-supplemented medium was caused by the mimicking of lysine control by hydroxylysine. Because hydroxylysine could not completely substitute for lysine and lysine could not be synthesized, the organism did not grow. We tested three lysine analogues and found that they prevented lysine-depletion lysis in the Lsy-OHLyss strain, as did hydroxylysine. Each analogue seemed to support cell wall mucopeptide synthesis, although ornithine did not. Preliminary data indicated that these analogues like hydroxylysine, have growth-inhibitory action on the Lys+OHLyss strain, but not the Lys+OHLysr strain. The nature of the specificity of the lysine-adding enzyme for cell wall mucopeptide synthesis is discussed. MATERIALS AND METHODS Compounds. L-Aspartic ,B-semialdehyde was prepared with the method used by Black and Wright (2). Diaminopimelic acid (DAP; a mixture of the LL and meso isomers) and a-aminoadipic acid-6-14C were obtained from Calbiochem (Los Angeles, Calif.). Aspartate-4-'4C, pyruvate-2-'4C,uniformly labeled "4C-L-lysine, and 5-hydroxylysine-6-'4C (mixture of four isomers) were obtained from the New England Nuclear Corp. (Boston, Mass.). a, e-DAP (labeled with tritium) was obtained from the Nuclear-Chicago Corp. (Des Plaines, Ill.). The lysine analogues 4, 5-trans-dehydrolysine, 2, 6-diamino-4-hexynoic acid, and L-thiosine [S-(,3-aminoethyl)-L-cysteine] were the generous gift of William Shive, Department of Chemistry, University of Texas. Cultures anid media. S. faecalis 8043 and two variants of this strain whose isolation was previously described (17) were used. The strains were designated 856

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“…We have recently found, however, that 2,6-diamino4-hexynoic acid (24), pK' = 8.4, can also generate rather high gradients across the plasma membrane of the Ehrlich cell, principally by System A. In this compound the two amino groups can scarcely approach each other.…”

mentioning

confidence: 99%

A cycle of deprotonation and reprotonation energizing amino-acid transport?

Christensen¹,

Handlogten²

1975

Proc. Natl. Acad. Sci. U.S.A.

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Although lowering the pK2 of neutral amino acids only weakens their concentrative uptake by Ehrlich cells, the same change greatly enhances uptake of diamino acids. This effect does not arise merely from putting the distal amino group in its uncharged form, but depends on an enhanced deprotonation of the a-amino group. Parallel effects are seen for the transport system for basic amino acids, for which the assignment of pK values within the membrane is less ambiguous. To explain the paradoxical advantages of having the a-amino group protonated yet readily deprotonated, we propose that a proton withdrawn from that group is pumped over an intramembrane interval to energize amino-acid transport.Although a driving of amino-acid uptake by cotransport with Na+ has long been known (1-4), this has recently been shown not to be the obligatory mode of energization (5). Furthermore, Na+-independent systems can unambiguously produce uphill transport (5). Therefore, we have long given attention to suggestive effects of modifying the H+-dissociation of the amino acids as clues to a more fundamental mode of energization (ref. 5; ref. 6, pp. 91-92; refs. 7-9). Table 1 illustrates that a systematic lowering of pK2' of neutral amino acids (in this case by introducing one, two, or three fluorine atoms) decreases both the initial rate of uptake and the steady-state distribution attained with Ehrlich ascites tumor cells. Fig. 1 shows a corresponding effect of the presence of two fluorine atoms in the amino-acid molecule: the pH optimum for uptake is lowered sharply. These results indicate that the amino acid is accepted for uptake by the system in question with the amino group in the form RNH3+ rather than RNH2. This result did not prove, however, that the recognition site at the interior surface of the membrane has the same preference. In 1958 we considered, using Fig. 2, whether a difference in the state of protonation preferred at the two surfaces might produce co-or countertransport of H+ with the amino acid (3). The figure shows a hydrogen ion left behind when the amino acid combines with the external receptor site, and a new hydrogen ion taken up by the amino acid on entering the cytoplasm. This scheme produces a countertransport between H+ and the amino acid, which was in 1958 an arbitrary choice over cotransport. Possibilities of this kind have subsequently become more important through the development by Mitchell of his chemiosmotic hypothesis for the intermediation of hydrogen ion gradients in the process of energy transduction by the mitochondrial and chloroplast membrane (11,12). The observation of cotransport of H+ with amino acids (see for example refs. 8 and 13) and with sugars (14-16) has accelerated the extension of these ideas to the plasma membrane (see ref. 17).Uptake of the lower homologs of lysine and ornithine By chance we encountered in 1952 behavior revealing that the data of Table 1 and Fig. 1 do not tell the whole story of the role of dissociation in amino-acid transport (18). The structural feature...

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2,6-Diamino-4-hexynoic acid, a lysine analog

Cited by 8 publications

References 5 publications

Studies with mechanism-based inactivators of lysine .epsilon.-transaminase from Achromobacter liquidum

Studies with mechanism-based inactivators of lysine .epsilon.-transaminase from Achromobacter liquidum

Effect of Hydroxylysine on the Biosynthesis of Lysine in Streptococcus faecalis

A cycle of deprotonation and reprotonation energizing amino-acid transport?

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