"A new method to determine the structure of the metal environment in
metalloproteins: investigation of the prion protein octapeptide repeat
Cu2+ complex"Matthias Mentler, Andreas Weiss, Klaus Grantner, Pablo del Pino, Dominga Deluca, Stella Fiori, Christian Renner, Wolfram Meyer Klaucke, Luis Moroder, Uwe Bertsch, Hans A. Kretzschmar, Paul Tavan, Fritz G. Parak
Eur. Biophys. J. 34, 97-112 (2005).
Since high-intensity synchrotron radiation is
available, ‘‘extended X-ray absorption fine structure’’
spectroscopy (EXAFS) is used for detailed structural
analysis of metal ion environments in proteins. However,
the information acquired is often insufficient to obtain an
unambiguous picture. ENDOR spectroscopy allows the
determination of hydrogen positions around a metal ion.
However, again the structural information is limited. In
the present study, a method is proposed which combines
computations with spectroscopic data from EXAFS,
EPR, electron nuclear double resonance (ENDOR) and
electron spin echo envelope modulation (ESEEM). From
EXAFS a first picture of the nearest coordination shell is
derived which has to be compatible with EPR data.
Computations are used to select sterically possible
structures, from which in turn structures with correct H
and N positions are selected by ENDOR and ESEEM
measurements. Finally, EXAFS spectra are re-calculated
and compared with the experimental data. This procedure
was successfully applied for structure determination
of the Cu2+ complex of the octapeptide repeat of the
human prion protein. The structure of this octarepeat
complex is rather similar to a pentapeptide complex
which was determined by X-ray structure analysis.
However, the tryptophan residue has a different orientation:
the axial water is on the other side of the Cu.
BMO authors (in alphabetic order):
Computation of structure, electrostatics, and conformational dynamics of PrPC induced by binding of Cu(II)