title: Swinging arms and swinging domains in multifunctional enzymes: catalytic machines for multistep reactions.
abstract: Multistep chemical reactions are increasingly seen as important in a growing number of complex biotransformations. Covalently attached prosthetic groups or swinging arms, and their associated protein domains, are essential to the mechanisms of active-site coupling and substrate channeling in a number of the multifunctional enzyme systems responsible. The protein domains, for which the posttranslational machinery in the cell is highly specific, are crucially important, contributing to the processes of molecular recognition that define and protect the substrates and the catalytic intermediates. The domains have novel folds and move by virtue of conformationally flexible linker regions that tether them to other components of their respective multienzyme complexes. Structural and mechanistic imperatives are becoming apparent as the assembly pathways and the coupling of multistep reactions catalyzed by these dauntingly complex molecular machines are unraveled.
authors.affiliation: Cambridge Centre for Molecular Recognition, Department of Biochemistry, University of Cambridge, Cambridge CB2 1GA, United Kingdom.
authors.forename: R N
authors.initials: RN
authors.lastname: Perham
mesh_terms: D000818:Animals; D001665:Binding Sites; D001710:Biotin / Q000378:metabolism; D002384:Catalysis; D006801:Humans; D008954:Models, Biological; D008958:Models, Molecular; D009097:Multienzyme Complexes / Q000737:chemistry* / Q000378:metabolism*; D010204:Pantetheine / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D017434:Protein Structure, Tertiary; D008063:Thioctic Acid / Q000378:metabolism
chemical_list: D009097:Multienzyme Complexes; D010204:Pantetheine; D001710:Biotin; D008063:Thioctic Acid