Target type: molecularfunction
Catalysis of the reaction: pyruvate + L-aspartate-4-semialdehyde = (2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinate + H2O. [PMID:8993314, RHEA:34171]
4-Hydroxy-tetrahydrodipicolinate synthase (HTPS) activity is a critical step in the biosynthesis of diaminopimelate (DAP), a key precursor for the synthesis of lysine and peptidoglycan, a major structural component of bacterial cell walls. HTPS catalyzes the condensation of L-aspartate semialdehyde and pyruvate to form 4-hydroxy-tetrahydrodipicolinate (HTPA), a central intermediate in the DAP biosynthesis pathway. The enzyme utilizes a highly conserved active site containing a pyridoxal phosphate (PLP) cofactor. The reaction mechanism involves the following key steps: 1) PLP forms a Schiff base with the amino group of L-aspartate semialdehyde. 2) The Schiff base is then deprotonated by a base, leading to the formation of a quinonoid intermediate. 3) The quinonoid intermediate undergoes nucleophilic attack by pyruvate, resulting in the formation of HTPA. 4) HTPA is released from the active site, and the enzyme returns to its initial state. The activity of HTPS is essential for bacterial growth and survival, making it a potential target for the development of novel antimicrobial agents.'
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Protein | Definition | Taxonomy |
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4-hydroxy-tetrahydrodipicolinate synthase | A 4-hydroxy-tetrahydrodipicolinate synthase that is encoded in the genome of Escherichia coli K-12. [PRO:DNx, UniProtKB:P0A6L2] | Escherichia coli K-12 |
Compound | Definition | Classes | Roles |
---|---|---|---|
alpha-ketobutyric acid | 2-oxobutanoic acid : A 2-oxo monocarboxylic acid that is the 2-oxo derivative of butanoic acid. alpha-ketobutyric acid: RN given refers to parent cpd; structure | 2-oxo monocarboxylic acid; short-chain fatty acid | |
glyoxylic acid | glyoxylic acid : A 2-oxo monocarboxylic acid that is acetic acid bearing an oxo group at the alpha carbon atom. glyoxylic acid: RN given refers to parent cpd | 2-oxo monocarboxylic acid; aldehydic acid | Escherichia coli metabolite; human metabolite; mouse metabolite; Saccharomyces cerevisiae metabolite |
3-fluoropyruvate | 3-fluoropyruvate : The anion of 3-fluoropyruvic acid. 3-fluoropyruvate: a substrate for E coli pyruvate dehydrogenase; structure; RN given refers to parent cpd 3-fluoropyruvic acid : A pyruvic acid derivative having a 3-fluoro substituent. | 2-oxo monocarboxylic acid; organofluorine compound | |
2-ketopentanoic acid | 2-ketopentanoic acid: RN given refers to parent cpd 2-oxopentanoic acid : An oxopentanoic acid carrying an oxo group at position 2. | 2-oxo monocarboxylic acid; oxopentanoic acid | human metabolite |