A selected ribozyme catalyzing diverse dipeptide synthesis.
The sequence of events by which protein, RNA, and DNA emerged during early biological evolution is one of the most profound questions regarding the origin of life. The contemporary role of aminoacyl-adenylates as intermediates in both ribosomal and nonribosomal peptide synthesis suggests that they may have served as substrates for uncoded peptide synthesis during early evolution. We report a highly active peptidyl transferase ribozyme family, isolated by in vitro selection, that efficiently catalyzes dipeptide synthesis by using an aminoacyl-adenylate substrate. It was characterized by sequence and structural analysis and kinetic studies. Remarkably, the ribozyme catalyzed the formation of 30 different dipeptides, the majority of rates being within 5-fold that of the Met-Phe dipeptide required by the selection. The isolation of this synthetic ribozyme fosters speculation that ribozyme-mediated uncoded peptide synthesis may have preceded coded peptide synthesis.
Sun
Lele
L
Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Cui
Zhiyong
Z
Gottlieb
Robert L
RL
Zhang
Biliang
B
D000249:Adenosine Monophosphate / Q000031:analogs & derivatives / Q000378:metabolism; D001483:Base Sequence; D001710:Biotin / Q000031:analogs & derivatives / Q000378:metabolism; D002384:Catalysis; D002851:Chromatography, High Pressure Liquid; D004151:Dipeptides / Q000096:biosynthesis*; D007700:Kinetics; D013058:Mass Spectrometry; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D009690:Nucleic Acid Conformation; D010453:Peptide Synthases / Q000737:chemistry / Q000378:metabolism; D010458:Peptidyl Transferases / Q000378:metabolism; D016337:RNA, Catalytic / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012335:RNA, Ribosomal / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
D004151:Dipeptides; D016337:RNA, Catalytic; D012335:RNA, Ribosomal; D000249:Adenosine Monophosphate; D001710:Biotin; D010458:Peptidyl Transferases; D010453:Peptide Synthases; C104385:non-ribosomal peptide synthase