InterPro: IPR015813 Pyruvate/Phosphoenolpyruvate kinase, catalytic core

Pyruvate kinase controls the exit from the glysolysis pathway, catalysing the transfer of phosphate from phosphooenolpyruvate (PEP) to ADP. Mammalian pyruvate kinase is a homotetramer, where each polypeptide subunit consists of four domains: N-terminal, A domain, B domain and C-terminal. Activation of the enzyme is believed to occur via the clamping down of the B domain onto the A domain to dehydrate the active site cleft. The N- and C-terminal domains are situated at inter-subunit contact sites, and could be involved in assembly and communication within the complex. The N-terminal domain has a TIM beta/alpha-barrel structure. Homologous TIM-barrel domains are found in the following proteins:

• N-terminal of pyruvate kinase (EC:2.7.1.40), which is interrupted by an all-beta domain [1].
• C-terminal of pyruvate phosphate dikinase (EC:2.7.9.1), which has a similar mode of substrate binding to pyruvate kinase [2].
• Phosphoenolpyruvate carboxylase (EC: 4.1.1.31); this domain has additional helices [3].
• Phosphenolpyruvate mutase(EC:5.4.2.9)/Isocitrate lyase (EC: 4.1.3.1), where it forms a swapped dimer [4].
• HpcH/HpaI aldolases, such as the beta subunit of citrate lyase, where it forms a swapped dimer, and contains a pyruvate kinase-type metal binding site [5].
• Ketopantoate hydroxymethyltransferase PanB (EC: 2.1.2.11), where a C-terminal helix exchange is observed in some enzymes [6].