InterPro domain: IPR039556

Proteins containing this domain are members of the ICL/PEPM enzyme family and catalyze either P-C or C-C bond formation/cleavage. Known members are phosphoenolpyruvate mutase (PEPM), phosphonopyruvate hydrolase (PPH), carboxyPEP mutase (CPEP mutase), oxaloacetate hydrolase (OAH), isocitrate lyase (ICL), and 2-methylisocitrate lyase (MICL) [ 1 , 2 , 3 ].

ICL catalyzes the conversion of isocitrate to succinate and glyoxylate, the first committed step in the glyoxylate pathway. This carbon-conserving pathway is present in most prokaryotes, lower eukaryotes and plants, but has not been observed in vertebrates [ 4 , 5 ].

PEPM turns phosphoenolpyruvate (PEP) into phosphonopyruvate (P-pyr), an important intermediate in the formation of organophosphonates, which function as antibiotics or play a role in pathogenesis or signaling. P-pyr can be hydrolyzed by phosphonopyruvate hydrolase (PPH) to from pyruvate and phosphate [ 6 , 7 ].

OAH catalyzes the hydrolytic cleavage of oxaloacetate to form acetate and oxalate, an important pathway to produce oxalate in filamentous fungi [ 8 ].

MICL cleaves 2-methylisocitrate to pyruvate and succinate, part of the methylcitrate cycle for the alpha-oxidation of propionate [ 8 ].

1. Crystal structure of DFA0005 complexed with alpha-ketoglutarate: a novel member of the ICL/PEPM superfamily from alkali-tolerant Deinococcus ficus. Proteins 73, 362-71
2. Structure and function of PA4872 from Pseudomonas aeruginosa, a novel class of oxaloacetate decarboxylase from the PEP mutase/isocitrate lyase superfamily. Biochemistry 47, 167-82
3. Insight into the mechanism of phosphoenolpyruvate mutase catalysis derived from site-directed mutagenesis studies of active site residues. Biochemistry 38, 14165-73
4. Characterization, gene cloning and expression of isocitrate lyase involved in the assimilation of one-carbon compounds in Hyphomicrobium methylovorum GM2. Eur. J. Biochem. 249, 820-5
5. Operation of glyoxylate cycle in halophilic archaea: presence of malate synthase and isocitrate lyase in Haloferax volcanii. FEBS Lett. 434, 13-6
6. Conformational flexibility of PEP mutase. Biochemistry 43, 4447-53
7. Properties of phosphoenolpyruvate mutase, the first enzyme in the aminoethylphosphonate biosynthetic pathway in Trypanosoma cruzi. J. Biol. Chem. 278, 22703-8
8. Crystal structures of 2-methylisocitrate lyase in complex with product and with isocitrate inhibitor provide insight into lyase substrate specificity, catalysis and evolution. Biochemistry 44, 2949-62