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Science 14 April 2006:
Vol. 312. no. 5771, pp. 273 - 276
DOI: 10.1126/science.1122928
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Reports

Conformational Switches Modulate Protein Interactions in Peptide Antibiotic Synthetases

Alexander Koglin,1 Mohammad R. Mofid,2* Frank Löhr,1 Birgit Schäfer,1 Vladimir V. Rogov,1,3 Marc-Michael Blum,1 Tanja Mittag,1{dagger} Mohamed A. Marahiel,2 Frank Bernhard,1 Volker Dötsch1{ddagger}

Protein dynamics plays an important role in protein function. Many functionally important motions occur on the microsecond and low millisecond time scale and can be characterized by nuclear magnetic resonance relaxation experiments. We describe the different states of a peptidyl carrier protein (PCP) that play a crucial role in its function as a peptide shuttle in the nonribosomal peptide synthetases of the tyrocidine A system. Both apo-PCP (without the bound 4'-phosphopantetheine cofactor) and holo-PCP exist in two different stable conformations. We show that one of the apo conformations and one of the holo conformations are identical, whereas the two remaining conformations are only detectable by nuclear magnetic resonance spectroscopy in either the apo or holo form. We further demonstrate that this conformational diversity is an essential prerequisite for the directed movement of the 4'-PP cofactor and its interaction with externally acting proteins such as thioesterases and 4'-PP transferase.

1 Institute of Biophysical Chemistry, Centre for Biomolecular Magnetic Resonance (BMRZ), J.W. Goethe University of Frankfurt, Marie-Curie-Strasse, D-60439 Frankfurt/Main, Germany.
2 Fachbereich Chemie-Biochemie, Philipps University of Marburg, Hans-Meerwein-Strasse D-35032 Marburg, Germany.
3 Institute of Protein Research, Puschino, Russia.

* Present address: Institute of Organic Chemistry, University of Munich, Munich, Germany.

{dagger} Present address: Structural Biology and Biochemistry, Hospital for Sick Children, 555 University Avenue, Toronto, Ontario M5G 1X8, Canada.

{ddagger} To whom correspondence should be addressed. E-mail: vdoetsch{at}em.uni-frankfurt.de

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THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
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Science. ISSN 0036-8075 (print), 1095-9203 (online)