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Volume 576, Issue 3, Pages 358-362 (22 October 2004)


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The SEP domain of p47 acts as a reversible competitive inhibitor of cathepsin L

Edited by Amy McGough

Michael Soukenikad, Anne Diehlab, Martina Leiderta, Volker Sievertbc, Konrad Büssowbc, Dietmar Leitnerab, Dirk Labuddeab, Linda J. Balla1, Annette Lechnere, Dorit K. Näglere, Hartmut OschkinatadCorresponding Author Informationemail address

Received 20 July 2004; received in revised form 13 September 2004; accepted 13 September 2004. published online 27 September 2004.

Abstract 

The solution structure of the human p47 SEP domain in a construct comprising residues G1-S2-p47(171–270) was determined by NMR spectroscopy. A structure-derived hypothesis about the domains' function was formulated and pursued in binding experiments with cysteine proteases. The SEP domain was found to be a reversible competitive inhibitor of cathepsin L with a Ki of 1.5 μM. The binding of G1-S2-p47(171–270) to cathepsin L was mapped by biochemical assays and the binding interface was investigated by NMR chemical shift perturbation experiments.

a Forschungsinstitut für Molekulare Pharmakologie, Robert-Rössle Str. 10, D-13125 Berlin, Germany

b Proteinstrukturfabrik, Berlin, Germany

c Max Planck Institut für Molekulare Genetik, Berlin, Germany

d Freie Universitaet Berlin, Berlin, Germany

e Department of Clinical Chemistry and Clinical Biochemistry, LMU Munich, Germany

Corresponding Author InformationCorresponding author. Fax: +493094793169

1 Present address: Structural Genomics Consortium, University of Oxford, Botnar Research Centre, OX37LD, UK.

PII: S0014-5793(04)01153-6

doi:10.1016/j.febslet.2004.09.037


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