Disease relevance of THR1

• Substrate specificity and identification of functional groups of homoserine kinase from Escherichia coli [1].
• Activation of these subunits occurs during late assembly stages through intramolecular precursor autolysis removing propeptides attached to Thr1, which then serves as N-terminal nucleophile in substrate hydrolysis [2].

High impact information on THR1

• A gallery of proteasome mutants that contain active site residues in the context of the inactive subunits beta3(Pup3), beta6(Pre7), and beta7(Pre4) show that the presence of Gly-1, Thr1, Asp17, Lys33, Ser129, Asp166, and Ser169 is not sufficient to generate activity [3].
• Tetrad analysis and genetic mapping established that integration occurs typically at the cup1(8) site located 28 centimorgans distal to thr1, a chromosome VIII marker [4].
• Thus, one role for the propeptides of active beta-type subunits might be to protect the mature subunits catalytic Thr1 alpha-amino group from acetylation [2].
• The modelled Thr1 side-chain is located above the gamma-turn bulge such that addition of its nucleophilic hydroxyl group to the electrophilic Gly-1 carbonyl carbon atom may proceed by very small motions [5].
• The same structure also supports addition of the Thr1 hydroxyl group to the carbonyl carbon atom of Leu-2 as a model for the first step in substrate hydrolysis by the proteasome [5].

Chemical compound and disease context of THR1

• Homoserine kinase, an enzyme in the aspartate pathway of amino acid biosynthesis in Escherichia coli, catalyzes the conversion of L-homoserine to L-homoserine phosphate [1].

Biological context of THR1

• Chromosome VIII disomes and trisomes were tagged with GFP (green fluorescent protein), DsRed (red fluorescent protein) and BFP (blue fluorescent protein) integrated at the thr1 locus, using our newly designed STIK (specific targeted integration of kanamycin resistance-associated, non-selectable DNA) plasmid system [6].
• This gene has been isolated from a yeast genomic library by complementation of a thr1 mutation [7].

Associations of THR1 with chemical compounds

• Disruption of the THR1 gene results in threonine auxotrophy in yeast [8].
• Saccharomyces cerevisiae homoserine kinase is homologous to prokaryotic homoserine kinases [8].
• The location of this residue was exploited for the rational design of bidentated inhibitors containing a maleinimide moiety at the P3 position for covalent linkage to the thiol group and a carboxy-terminal aldehyde group for hemiacetal formation with the Thr1 hydroxyl group of the active site [9].

Other interactions of THR1

• In a BOR3 mutant, THR1, HOM2 and HOM3 mRNA levels were increased slightly [10].
• The presence of three canonical GCN4 regulatory sequences in the upstream flanking region suggests that the expression of THR1 is under the general amino acid control [11].

Analytical, diagnostic and therapeutic context of THR1

• By genetic crosses and tetrad analysis it has been demonstrated that integration has occurred at the THR1 locus [7].
• In parallel, the enzyme was purified by four consecutive column chromatographies, monitoring homoserine kinase activity [11].

References