Table 3 Structural characteristics of various enzymes targeted by amino acid feedback inhibition

Dihydrodipicolinate synthase (DHDPS)

L-lysine

Diaminopimelic acid pathway (DAP)

i. Either as dimer or tetramer (more stable)

ii. DHDPS has different level of sensitivity towards L-lysine based on its source/origin

iii. DHDPS of gram-negative are lysine-sensitive and DHDPS of gram-positive are lysine-insensitive

[68, 139,140,141,142,143,144,145,146,147,148,149]

Homoserine O-acetyltransferase (HTA)

L-methionine

Aspartate biosynthetic pathway; Branched methionine biosynthetic pathway

Comprises of two domain

i. core α/β-domain (comprising of eight strands; parallel β-sheets β1, β4–β10 connected to five α-helices on one side and one on other side

ii. Helical bundle domain (composed of five α-helices) that form a lid over core domain

iii. tunnel at interface of two domains that serve as channel for transfer of substrate to active site

[150,151,152,153,154]

chorismate mutase/prephenate dehydrogenase (TyrA)

Tyrosine

Aromatic amino acids biosynthesis (i.e. tyrosine)

i. Homodimer where N-terminal CM domain catalyzes conversion (Claisen rearrangement) of chorismate to prephenate that is later converted to 4-hydroxyphenylpyruvate through C-terminal PDH domain

ii. Dimer in case of H. influenza where each monomer consists of N-terminal: NAD⁺ binding site and C-terminal α-helical dimerization domain

iii. Tyrosine being competitive inhibitor binds directly inside active site

[116, 155, 156]

Serine acetyltransferase (SAT)

Cysteine

cysteine biosynthesis

i. Exists as monomer, trimer and hexamer

ii. Monomer comprises of two domains i.e. (i). α-helical domain (residues 1–140), (ii). β-helical domain (residues 141–262)

iii. Monomer structural units pack together to form trimer structure and ultimately hexamer structure

iv. cysteine binding site is located at interface of two subunits

[48, 157,158,159]

3-phosphoglycerate dehydrogenase

Phosphoserine phosphatase (PSP)

L-serine

Glycolate and phosphorylated pathway

i. Homotetrameric structure comprising of four active sites alongside four effector binding sites

ii. Ligand/inhibitor binding site lies in regulatory domain region

iii. PGDH_Mt exits in three different forms i.e. homodimer, homotetramer, homooctamer

iv. Different level of sensitivity towards L-serine inhibition

[160,161,162,163,164,165,166,167]

Pyrroline-5-carboxylate synthase

Glutamate kinase (GK)

Proline

i. Exists as dimer, tetramer and hexamer structure

ii. Feedback inhibition of GK by proline is not affected by oligomeric structure

iii. Different arrangements of subunits are observed for dimers in case of C. jejuni and E.coli

[60, 168, 169]