title: Metabolic channelling of carbamoyl phosphate in the hyperthermophilic archaeon Pyrococcus furiosus: dynamic enzyme-enzyme interactions involved in the formation of the channelling complex.
abstract: Protection of thermolabile metabolites and coenzymes is a somewhat neglected but essential aspect of the molecular physiology of hyperthermophiles. Detailed information about the mechanisms used by thermophiles to protect these thermolabile metabolites and coenzymes is still scarce. A case in point is CP (carbamoyl phosphate), a precursor of pyrimidines and arginine, which is an extremely labile and potentially toxic intermediate. Recently we obtained the first evidence for a physical interaction between two hyperthermophilic enzymes for which kinetic evidence had suggested that these enzymes channel a highly thermolabile and potentially toxic intermediate. By physically interacting with each other, CKase (carbamate kinase) and OTCase (ornithine carbamoyltransferase) prevent thermodenaturation of CP in the aqueous cytoplasmic environment. The CP channelling complex involving CKase and OTCase or ATCase (aspartate carbamoyltransferase), identified in hyperthermophilic archaea, provides a good model system to investigate the mechanism of metabolic channelling and the molecular basis of protein-protein interactions in the physiology of extreme thermophiles.
authors.affiliation: Laboratorium voor Erfelijkheidsleer en Microbiologie, Vrije Universiteit Brussel, Pleinlaan 2, B-1050 Brussels, Belgium. jan.massant@vub.ac.be
authors.forename: J
authors.initials: J
authors.lastname: Massant
authors.forename: N
authors.initials: N
authors.lastname: Glansdorff
mesh_terms: D001120:Arginine / Q000737:chemistry; D001221:Aspartate Carbamoyltransferase / Q000737:chemistry; D001669:Biochemical Phenomena; D001671:Biochemistry; D002221:Carbamyl Phosphate / Q000737:chemistry*; D018360:Crystallography, X-Ray; D003593:Cytoplasm / Q000378:metabolism; D006358:Hot Temperature; D007700:Kinetics; D008956:Models, Chemical; D009954:Ornithine Carbamoyltransferase / Q000737:chemistry; D017851:Phosphotransferases (Carboxyl Group Acceptor) / Q000737:chemistry; D011485:Protein Binding; D011487:Protein Conformation; D011743:Pyrimidines / Q000737:chemistry; D020027:Pyrococcus furiosus / Q000201:enzymology*; D013696:Temperature
chemical_list: D011743:Pyrimidines; D002221:Carbamyl Phosphate; D001120:Arginine; D001221:Aspartate Carbamoyltransferase; D009954:Ornithine Carbamoyltransferase; D017851:Phosphotransferases (Carboxyl Group Acceptor); C019288:carbamate kinase; C030986:pyrimidine