Protein splicing: how inteins escape from precursor proteins.
Inteins are nature's escape artists; they facilitate their excision from flanking polypeptides (exteins) concomitant with extein ligation to produce a mature host protein. Splicing requires sequential nucleophilic displacement reactions catalyzed by strategies similar to proteases and asparagine lyases. Inteins require precise reaction coordination rather than rapid turnover or tight substrate binding because they are single turnover enzymes with covalently linked substrates. This has allowed inteins to explore alternative mechanisms with different steps or to use different methods for activation and coordination of the steps. Pressing issues include understanding the underlying details of catalysis and how the splicing steps are controlled.
From the Department of Chemistry, College of the Holy Cross, Worcester, Massachusetts 01610.
Kenneth V
KV
Mills
the Department of Chemistry, University of Alabama at Birmingham, Birmingham, Alabama 35294, and.
Margaret A
MA
Johnson
New England Biolabs, Inc., Ipswich, Massachusetts 01938 perler@neb.com.
Francine B
FB
Perler
D000596:Amino Acids / Q000737:chemistry / Q000235:genetics; D047669:Exteins / Q000235:genetics; D047668:Inteins / Q000235:genetics*; D008957:Models, Genetic; D015394:Molecular Structure; D011498:Protein Precursors / Q000737:chemistry / Q000235:genetics*; D019154:Protein Splicing / Q000235:genetics*; D011506:Proteins / Q000737:chemistry / Q000235:genetics
D000596:Amino Acids; D011498:Protein Precursors; D011506:Proteins
Asparagine Cyclization; Bacterial Intein-like Domain; Enzyme Kinetics; Enzyme Mechanisms; Hedgehog; Intein; Post-translational Modification; Protein Motifs; Protein Splicing; Thioester