Swapping structural determinants of ribonucleases: an energetic analysis of the hinge peptide 16-22.
Bovine seminal ribonuclease (BS-RNase) is a homodimeric enzyme strictly homologous to the pancreatic ribonuclease (RNase A). Native BS-RNase is an equilibrium mixture of two distinct dimers differing in the interchange of the N-terminal segments and in their biological properties. The loop 16-22 plays a fundamental role on the relative stability of the two isomers. Both the primary and tertiary structures of the RNase A differ substantially from those of the seminal ribonuclease in the loop region 16-22. To analyze the possible stable conformations of this loop in both enzymes, structure predictions have been attempted, according to a procedure described by Palmer and Scheraga [Palmer, K. A. & Scheraga, H. A. (1992) J. Comput. Chem. 13, 329-350]. Results compare well with experimental x-ray structures and clarify the structural determinants that are responsible for the swapping of the N-terminal domains and for the peculiar properties of BS-RNase. Minimal modifications of RNase A sequence needed to form a stable swapped dimer are also predicted.
Mazzarella
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Centro di Studio di Biocristallografia, Università di Napoli Federico II, Naples, Italy.
Vitagliano
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Zagari
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A
D000818:Animals; D002417:Cattle; D046911:Macromolecular Substances; D008297:Male; D008958:Models, Molecular; D010446:Peptide Fragments / Q000737:chemistry*; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D012260:Ribonucleases / Q000737:chemistry* / Q000378:metabolism*; D012661:Semen / Q000201:enzymology; D013816:Thermodynamics
D046911:Macromolecular Substances; D010446:Peptide Fragments; D012260:Ribonucleases