Structural insights into the mechanism of intramolecular proteolysis.
A variety of proteins, including glycosylasparaginase, have recently been found to activate functions by self-catalyzed peptide bond rearrangements from single-chain precursors. Here we present the 1.9 A crystal structures of glycosylasparaginase precursors that are able to autoproteolyze via an N --> O acyl shift. Several conserved residues are aligned around the scissile peptide bond that is in a highly strained trans peptide bond configuration. The structure illustrates how a nucleophilic side chain may attack the scissile peptide bond at the immediate upstream backbone carbonyl and provides an understanding of the structural basis for peptide bond cleavage via an N --> O or N --> S acyl shift that is used by various groups of intramolecular autoprocessing proteins.
Xu
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Department of Biophysics, Boston University School of Medicine, Massachusetts 02118-2526, USA.
Buckley
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Guan
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Guo
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HC
D001227:Aspartylglucosylaminase / Q000378:metabolism*; D001665:Binding Sites; D018360:Crystallography, X-Ray; D005417:Flavobacterium / Q000201:enzymology; D005998:Glycine / Q000378:metabolism; D007700:Kinetics; D008956:Models, Chemical; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016296:Mutagenesis; D011485:Protein Binding; D011487:Protein Conformation; D011498:Protein Precursors / Q000378:metabolism*; D017434:Protein Structure, Tertiary
D011498:Protein Precursors; D001227:Aspartylglucosylaminase; D005998:Glycine