TY - JOUR
T1 - Synthetic human prion protein octapeptide repeat binds to the proteinase K active site
AU - Georgieva, Dessislava
AU - Rypniewski, Wojciech
AU - Echner, Hartmut
AU - Perbandt, Markus
AU - Koker, Mirjam
AU - Clos, Joachim
AU - Redecke, Lars
AU - Bredehorst, Reinhard
AU - Voelter, Wolfgang
AU - Genov, Nicolay
AU - Betzel, Christian
N1 - Funding Information:
The authors thank the Deutsche Luft- und Raumfahrtagentur (DLR, Projektträger Gesundheitsforschung, Grant 01KO0206) and the RiNA GmbH Berlin for financial support. This work was supported in part by the Bulgarian National Foundation for Scientific Research, Grant X-1301. Ch. Betzel thanks the Deutsche Forschungsgemeinschaft for the financial support during a visit at the Institute of Organic Chemistry, Bulgarian Academy of Sciences, under contract 436 BUL 113/115/8-1.
Copyright:
Copyright 2012 Elsevier B.V., All rights reserved.
PY - 2004/12/24
Y1 - 2004/12/24
N2 - 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 1.8 Å 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 β-strand between the two parallel strands of Asn99-Tyr104 and Ser132-Gly136. The complex is stabilized through an extended H-bonding network.
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 1.8 Å 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 β-strand between the two parallel strands of Asn99-Tyr104 and Ser132-Gly136. The complex is stabilized through an extended H-bonding network.
UR - http://www.scopus.com/inward/record.url?scp=8844276881&partnerID=8YFLogxK
U2 - 10.1016/j.bbrc.2004.10.184
DO - 10.1016/j.bbrc.2004.10.184
M3 - Journal articles
C2 - 15555583
AN - SCOPUS:8844276881
SN - 0006-291X
VL - 325
SP - 1406
EP - 1411
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 4
ER -
