NR ARHD
AU Georgieva,D.; Rypniewski,W.; Echner,H.; Perbandt,M.; Koker,M.; Clos,J.; Redecke,L.; Bredehorst,R.; Voelter,W.; Genov,N.; Betzel,C.
TI Synthetic human prion protein octapeptide repeat binds to the proteinase K active site
QU Biochemical and Biophysical Research Communications 2004 Dec 24; 325(4): 1406-11
PT journal article
AB Proteinase K is widely used in tests for the presence of infectious prion protein causing fatal spongiform encephalopathies. To investigate possible interactions between the enzyme and the functionally important N-terminal prion domain, we crystallized mercury-inhibited proteinase K in the presence of the synthetic peptides GGGWGQPH and HGGGW. The octapeptide sequence is identical to that of a single octapeptide repeat (OPR) from the physiologically important OPR region. Here, we present the first direct evidence for the complex formation between a proteolytic enzyme and a segment of human prion molecule. The X-ray structures of the complexes at 1.4 and 1.8A resolution, respectively, revealed that in both cases the segment GGG is strongly bound as a real substrate at the substrate recognition site of the proteinase forming an antiparallel beta-strand between the two parallel strands of Asn99-Tyr104 and Ser132-Gly136. The complex is stabilized through an extended H-bonding network.
MH Binding Sites; Comparative Study; Computer Simulation; Crystallography, X-Ray/*methods; Dimerization; Endopeptidase K/*chemistry; Enzyme Activation; Humans; *Models, Chemical; *Models, Molecular; Multiprotein Complexes/chemistry; Peptides/*chemistry; Prions/*chemistry; Protein Binding; Protein Conformation; Protein Structure, Secondary; Protein Structure, Tertiary; Research Support, Non-U.S. Gov't; Structure-Activity Relationship; Substrate Specificity
AD Zentrum für Experimentelle Medizin, Institut für Biochemie und Molekularbiologie I, Universitätsklinikum Hamburg-Eppendorf, c/o DESY, Notkestrasse 85, Geb. 22a, 22603 Hamburg, Germany.
SP englisch
PO USA