Methylaspartate

Pip = D-pipecolic acid MeAsp = A -methylaspartic acid. The amphomycin family member having (+)-3-anteisotridecenoic acid is shown not shown is... 

Nodularia spwnigena has also been shown to produce a peptide with hepato-toxic activity. The more recent reports come from Australia (76), the German Democratic Republic (77), Denmark (78), Sweden (79), and Finland (80,81). Recently structure information on Nodularia toxin has been presented by Rinehart (97) for waterbloom material collected in Lake Forsythe, New Zealand, in 1984 by Eriksson et al. (81) from waterbloom material collected in the Baltic Sea in 1986, and Runnegar et al. (82) for a field isolate from the Peel Inlet, Perth, Australia. Structure work by Rinehart, Eriksson, and Runnegar all indicate that the peptide is smaller than the heptapeptide toxins. Rinehart s work (97) indicates the toxin is a pentapeptide with a similar structure to the heptapeptides and containing fi-methylaspartic acid, glutamic acid, arginine, dehydrobutyrine, and ADDA (MW 824). 

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. 

METHYLASPARTATE AMMONIA-LYASE N-METHYLGLUTAMATE SYNTHASE UREASE... 

METHYLASPARTATE AMMONIA-LYASE B-METHYLASPARTATE-GLUTAMATE MUTASE... 

One substance that has been found to be an essential requirement for the biosynthesis of DNA is the cobalt-containing vitamin B12 (42). Ever since this substance was first isolated and its structure determined, there has been a widespread search for the specific reactions that it mediates. The first such reaction was discovered by Barker, Weissbach, and Smyth (5), when they examined the enzymatic isomerization of glutamic acid to /3-methylaspartic acid. They were... 

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)...

C) Nine sections, spaced 0.1 nm apart, of a part of the 2-methylaspartate difference map superimposed on the atomic model shown in (A) and... 

D). The coenzyme is shown as the internal aldimine with Lys 258 (see Fig. 14-6,14-10). The positive and negative contours on the two sides of the coenzyme ring indicate that the coenzyme tilts over to form the external aldimine when substrates react.413 (D) Superimposed structure of the active site of the enzyme in its free form as in (A) (bold lines) and the refined structure of the a-methylaspartate complex, (dashed lines).411 This illustrates the tilting of the coenzyme ring, which is also shown in Eq. 14-39 and Fig. 14-10. Courtesy of Arthur Amone and Sangkee Rhee. 

Fig. 25-15). In every case it is NH3 or an amine, rather than an OH group, that is eliminated. However, the mechanisms probably resemble that of fumarate hydratase. Sequence analysis indicated that all of these enzymes belong to a single fumarase-aspartase family.64 65 The three-dimensional structure of aspartate ammonia-lyase resembles that of fumarate hydratase, but the catalytic site lacks the essential HI 88 of fumarate hydratase. However, the pKa values deduced from the pH dependence of Vmax are similar to those for fumarase.64 3-Methylaspartate lyase catalyzes the same kind of reaction to produce ammonia plus czs-mesaconate.63 Its sequence is not related to that of fumarase and it may contain a dehydroalanine residue (Chapter 14).66... 

Figure 23-9 Polarized absorption spectra of orthorhombic crystals of cytosolic aspartate aminotransferase. The light beam passed through the crystals along the b axis with the plane of polarization parallel to the a axis (A) or the c axis (C). Left, native enzyme at pH 5.4 right, enzyme soaked with 300 mM 2-methylaspartate at pH 5.9. The band at 430 nm represents the low pH proto-nated Schiff base form of the enzyme. Upon soaking with 2-methylaspartate the coenzyme rotates 30° to form a Schiff base with this quasisubstrate. The result is a large change in the c/a polarization ratio. The 364 nm band in the complex represents the free enzyme active site in the second subunit of the dimeric enzyme.70,73 Courtesy of C. M. Metzler.

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

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