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PMID: 15498563 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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

FEBS letters ·Vol. 576 ·No. 3 ·2004-10-22 ·Pages 358-62

Soukenik M, Diehl A, Leidert M, Sievert V, Büssow K, Leitner D, Labudde D, Ball LJ, Lechner A, Nägler DK, Oschkinat H

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 microM. 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.

MeSH Terms
Amino Acid Sequence Base Sequence Binding Sites Cathepsin B/chemistry,metabolism Cathepsin K Cathepsin L Cathepsins/antagonists & inhibitors,chemistry,metabolism Cysteine Endopeptidases Cysteine Proteinase Inhibitors/pharmacology DNA Primers Humans Kinetics Magnetic Resonance Spectroscopy Models, Molecular Molecular Sequence Data Peptide Fragments/pharmacology Protein Structure, Secondary Sequence Alignment Sequence Homology, Amino Acid
Chemicals
Cysteine Proteinase Inhibitors DNA Primers Peptide Fragments Cathepsins Cysteine Endopeptidases Cathepsin B CTSL protein, human Cathepsin L CTSK protein, human Cathepsin K
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Soukenik Michael
Forschungsinstitut für Molekulare Pharmakologie, Robert-Rössle Str. 10, D-13125 Berlin, Germany.
Diehl Anne
Leidert Martina
Sievert Volker
Büssow Konrad
Leitner Dietmar
Labudde Dirk
Ball Linda J
Lechner Annette
Nägler Dorit K
Oschkinat Hartmut
Article Info
Journal
FEBS letters
Abbr.
FEBS Lett
ISSN
0014-5793
Published
2004-10-22
Pages
358-62
Language
English
Region
England
NLM ID
0155157
Subset
IM
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