Homoserine kinase activation

R234C <4> (<4>, no observable homoserine kinase activity, the ATPase activity is nearly 20times that of the wild-type enzyme at pH 8.0. 7fold increase... 

H139L <4> (<4>, mutant enzyme with diminished kinase activity and ATPase activity 150fold greater than that of the wild-type enzyme [12]) [12] H202L <4> (<4>, Km-value for L-homoserine and ATP remain unchanged, the K -value for substrate inhibition by L-homoserine increases about 8fold, the turnover-number decreases by 50%, unlike the wild-type enzyme the L-homoserine ethyl, isopropyl, and n-propyl esters show substrate inhibition [12]) [12]... 

Patte, J.C. Clepet, C. Bally, M. Borne, R Mejean, V Foglino, M. ThrH, a homoserine kinase isozyme with in vivo phosphoserine phosphatase activity in Pseudomonas aeruginosa. Microbiology, 145, 845-853 (1999)... 

Homoserine kinase hsis been enriched about fifteen- to twenty-fivefold from brewer s yeast extracts (106,107). ATP is essential for the reaction, as would be smticipated, and evidence was obtained of activation by Mg++, Mn , or Zn++. Enzyme activity was found to be inhibited by ethylene-diaminetetraacetate (EDTA) and p-chloromercuribenzoate (106). 

Aspartate kinase [EC 2.T.2.4], also known as asparto-kinase, catalyzes the reaction of aspartate with ATP to produce 4-phosphoaspartate and ADP. The enzyme isolated from E. coli is a multifunctional protein, also exhibiting the ability to catalyze the reaction of homoserine with NAD(P) to produce aspartate 4-semialdehyde and NAD(P)H (that is, the activity of homoserine dehydrogenase, EC 1.1.1.3). 

As noted, another possiblity is that the changes in essential amino add synthetic capadty in isolated plastids are due to fluctuations in the catalytic activity [1] of key regulatory enzymes (see Fig. 1). Indeed, in preliminary experiments we have found aspartate kinase [14] and homoserine dehydrogenase [15] activity in plastids from 8 day old pea plants to be 2-6 times greater than in those from 14 day old plants (data not shown). Nonetheless, additional purification and immunological studies will be required to confirm these results. 

The cells could produce even more lysine if the kinase were to remain active but insensitive to a high lysine concentration. Mutants of the homoserine auxotrophs of C. glutamicum were isolated with this property by growing the organism in the presence of toxic isosteres (close structural analogues) of lysine (e.g. S-(2-aminoethyl)-L-cysteine). One way in which the cells can become resistant to the toxic isostere is to overproduce lysine. This is likely to occur in cells where the mutation alters aspartyl kinase in such a way as to make it insensitive to inhibition by lysine, while allowing it to retain its full catalytic activity. 

Isoenzymes of enzymes involved in the first step of a branched biosynthetic pathway may differ in their sensitivity to inhibitors. Thus the enzyme aspartate kinase catalyses in Escherichia coli the first step in the synthesis of lysine, methionine and threonine. Three isoenzymes occur, the synthesis and activity of one is suppressed by L-lysine, the activity of the second is depressed by L-threonine and the activity of the third by homoserine (an intermediate in methionine biosynthesis). Thus accumulation of L-lysine or L-threonine suppresses their own further S3mthesis but does not prevent the activity of the aspartokinase isoenzyme involved in methionine synthesis. Again peroxidase isoenzymes differ in their activity in destroying indol-3yl-acetic acid (lAA) and the pattern of peroxidase isoenzymes can be altered by feeding lAA or gibberellic acid (GA) to plant tissues. 

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