Phosphoenolpyruvate/pyruvate domain superfamily

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 , which is interrupted by an all-beta domain [11563914].
• C-terminal of pyruvate phosphate dikinase , which has a similar mode of substrate binding to pyruvate kinase [11790099].
• Phosphoenolpyruvate carboxylase ; this domain has additional helices [12467579].
• Phosphenolpyruvate mutase/Isocitrate lyase , where it forms a swapped dimer [11526312].
• 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 [7064730].
• Ketopantoate hydroxymethyltransferase PanB , where a C-terminal helix exchange is observed in some enzymes [12906829].