title: Structure-function relationships in RNA and RNP enzymes: recent advances.
abstract: The structural biology of ribozymes and ribonucleoprotein (RNP) enzymes is now sufficiently advanced that a true dialogue between structural and functional studies is possible. In this review, we consider three important systems in which an integration of structural and biochemical data has recently led to major advances in mechanistic understanding. In the hammerhead ribozyme, application-driven biochemical studies led to the discovery of a key structural interaction that had been omitted from previously-studied constructs. A new crystal structure of the resulting, tertiary-stabilized hammerhead has resolved a remarkable number of longstanding paradoxes in the structure-function relationship of this ribozyme. In the Group I intron ribozyme, a flurry of high-resolution structures has largely confirmed, but in some cases refined or challenged, a detailed model of a metalloenzyme active site that had previously been derived by meticulous quantitative metal ion rescue experiments. Finally, for the peptidyl transferase center of the ribosome, recent biochemical and chemical results motivated by the pioneering crystal structures have suggested a picture of a catalytic mechanism dominated by proximity and orientation effects and substrate-assisted catalysis. These results refocus attention on catalysis as a property of the integrated RNP machinery as a whole, as opposed to a narrow concern with the RNA functional groups in immediate contact with the reactive center.
authors.affiliation: Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI 48824, USA. hoogstr3@msu.edu
authors.forename: Charles G
authors.initials: CG
authors.lastname: Hoogstraten
authors.forename: Minako
authors.initials: M
authors.lastname: Sumita
mesh_terms: D002384:Catalysis; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D017434:Protein Structure, Tertiary; D012313:RNA / Q000737:chemistry*; D016337:RNA, Catalytic / Q000737:chemistry*; D012261:Ribonucleoproteins / Q000737:chemistry*; D013329:Structure-Activity Relationship