L-/ -Methylaspartate

D-ervf/iro-V7-(tert-Butoxycarbonyl)-(l-methylaspartic Acid a-Methyl Ester (75) 2T ... 

C4. Cedrangolo, F., Della Pietra, G., Cittadini, D., Papa, S., and De Lorenzo, F., Urea synthesis in rats treated with a-D,L-methylaspartic acid. Nature (London) 196, 708-709 (1962). 

Bright (1964) has studied the mechanism of the j3-methylaspartase reaction, in which the enzyme /S-methylaspartase catalyzes the reversible conversion of L-/ -methylaspartate (LXXXVI) to mesaconate (LXXXVII) and ammonia ... 

This cobalamin-dependent enzyme [EC 4.3.1.2], also known as /3-methylaspartase, catalyzes the conversion of L-r/ireo-3-methylaspartate to mesaconate and ammonia. 

Figure 3-23 (A) Stereoscopic a-carbon plot of the cystolic aspartate aminotransferase dimer viewed down its dyad symmetry axis. Bold lines are used for one subunit (subunit 1) and dashed lines for subunit 2. The coenzyme pyridoxal 5 -phosphate (Fig. 3-24) is seen most clearly in subunit 2 (center left). (B) Thirteen sections, spaced 0.1 nm apart, of the 2-methylaspartate difference electron density map superimposed on the a-carbon plot shown in (A). The map is contoured in increments of 2a (the zero level omitted), where a = root mean square density of the entire difference map. Positive difference density is shown as solid contours and negative difference density as dashed contours. The alternating series of negative and positive difference density features in the small domain of subunit 1 (lower right) show that the binding of L-2-methylaspartate between the two domains of this subunit induces a right-to-left movement of the small domain. (Continues)...

In fact, their endeavours were rewarded by a double discovery that of AdoCbl, and also the first AdoCbl-dependent enzymic rearrangement - the reversible interconversion of L-glutamate and (2S,3S)-3-methylaspartate (Fig. 2). 

The microcystins are a group of over 70 structurally related monocyclic heptapeptides containing seven peptide-linked aminoacids with the general structure of Cyclo-(D-alanine -X -D-MeAsp -Y" -Adda -D-glutamate - Mdha ), in which X and Y are variable L aminoacids, D-MeAsp is D-erytro- - methylaspartic acid and Mdha is N-methyldehydroalanine (Fig. 14.1). 

Wetmore SD, Smith DM, Golding BT, Radom L. Interconversion of (S)-glntamate and (2S,3S)-3-methylaspartate a distinctive B-12-dependent carbon-skeleton rearrangement. J. Am. Chem. Soc. 2001 123 7963-7972. 

Freshwater cyanobacteria Microcystis, Oscillatoria, Ana-baena, and Nostoc produce several types of toxins, among which the most commonly detected are the hepatotoxic peptides microcystins. The general structure of the microcystins is cyclo-(D-Ala -X -D-MeAsp -Z -Adda -D-Glu -Mdha ), in which X and Z represent variable L-amino acids, D-MeAsp is D-eryf/iro-p-methylaspartic acid, Mdha is A-methyldehydroalanine, and Adda is the unusual C20 amino acid, (25,35,85,95)-3-amino-9-meth-oxy-2,6,8-trimethyl-10-phenyldeca-4( ),6( )-dienoic acid (Fig. 1). The structural differences in the microcystins mainly depend on the variability of the two L-amino acids (denoted X and Z), and secondarily on the methylation or demethylation of D-MeAsp and/or Mdha. More than 60 microcystins have been isolated from bloom samples and isolated strains of cyanobacteria. 

Fig. 7. Structure of one member of the amphomycin family where Dabe = D-erythro-a, /3-diaminobutyric acid Dab1 = l-threo-oc, /3-diaminobutvric acid Pip = D-pipecolic acid MeAsp = AT-methylaspartic acid. The amphomycin family member having (+)-3-anteisotridecenoic acid is shown not shown is...

PAL/TAL both belong to the L-amino acid ammonia lyase family, which catalyzes the formation of various a,/3-unsaturated acids by elimination of ammonia (ammonium ion) from the corresponding L-ct-amino acids. This family of proteins includes aspartate ammonia lyase (AAL), methylaspartate ammonia lyase (MAL), HAL,... 

Figure 20 Cartoon representation of the active site of dimeric pig cytosolic AAT (subunits are colored in magenta and cyan) in complex with L-2-methylaspartate, in which the external aldimine of PLP and the amino acid residues cited in the text are represented by a stick model.

Microcystins constitute a large family of cyclic heptapeptides with a high degree of homology in the amino acid sequence. As shown in Fig. 4, they are composed of D-Ala in position 1, two variable L-amino acids at positions 2 and 4, the 3-linked D-e/yt/iro-P-methylaspartic acid (MeAsp) in position 3, the novel C20 P-amino acid (25,35,85,95) - 3 - amino - 9-methoxy-2,6,8-trimethyl-10-phenyldeca-4,6-dienoic acid... 

Amino-acid analogs and uncommon L-amino acids W-acetyl-aspartate, W-acetyl-serine, oi-amino-n-butyrate, 3-aminoisobutyrate, aspartate ethyl or methyl ester, citrulline, cysteate, fumarate, glutathione, homoserine, erythro- and threo-p-hydroxyaspartate, isoasparagine, isoserine, malate, a- and p-methylaspartate, methylserine, phenol, serine amide, serine methyl ester, succinate [498, 747]... 

The chiroptical properties of a-methyl-a-amino acids have been investigated (Yamada et al, 1969 Shoji, 1973 Weinges and Stemmle, 1973 Goux et al, 1974), and the 210-nm positive n-7r Cotton effect has been correlated with the L configuration as in the case of the simple a-amino acids. An exception to this rule is L-a-methylaspartic acid, which shows a negative Cotton effect in acid (at 200 nm) and in alkali (at 222 nm) a positive Cotton effect is observed in water. Attempts have been made to interpret these results (Yamada et al, 1969). 

Figure 1. Structure of the blue-green algal toxin microcystin-LR. Besides the two variable L-amino acids, leucine and arginine, the microcystin contains three D-amino acids (glutamic acid, alanine and methylaspartic acid) and two unusual amino acids, N-methyl-dehydroalanine (Mdha) and 3-amino-9-methoxy-2,6,8-trimethyl-10-phenyl-deca-4,6-dienoic acid (Adda) (see Ref. 4).

Microcystins (Figure lA) are cyclic heptapeptides of low molecular weight quite frequently implicated in intoxication events and synthesized by the cyanobacteria genera such as Microcystis, Anabaena, Planktothrix, and Nostoc. They contain two unusual amino-acids N-methyl-dehydroalanine (Mdha) and 3-amino-9-met-hoxy-2,6,8-trimethyl-10-phenyl-4,6-dienoic add (ADDA). The most common sequence is o-Ala -L-X -o-Masp -L-Z" -Adda -D-Glu -Mdha, where Masp stands for methylaspartic acid and X and Z for two variable... 

Methylaspartase from Clostridium tetanomorphum catalyses the stereospecific addition of ammonia to mesaconic acid (23) to yield (2S,3S)-3-methylaspartic acid (24). The latter can then be converted to the isosteric L-valine analogue (2/ , 3/l)-3-bromobutyrine (25) (Scheme 5.21). 

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