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  Structures of the tricorn-interacting aminopeptidase F1 with different ligands explain its catalytic mechanism

Goettig, P., Groll, M., Kim, J. S., Huber, R., & Brandstetter, H. (2002). Structures of the tricorn-interacting aminopeptidase F1 with different ligands explain its catalytic mechanism. EMBO Journal, 21(20), 5343-5352.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0010-6E1A-7 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0010-6E1B-5
Genre: Journal Article
Alternative Title : Embo J.

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 Creators:
Goettig, P.1, 2, Author              
Groll, M.2, Author              
Kim, J. S.2, Author              
Huber, R.2, Author              
Brandstetter, H.2, Author              
Affiliations:
1Fässler, Reinhard / Molecular Medicine, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565147              
2Huber, Robert / Structure Research, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565155              

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Free keywords: biological rectifier; caged active site; gating mechanism; prolyl peptidases; substrate channelling
 Abstract: F1 is a 33.5 kDa serine peptidase of the alpha/beta-hydrolase family from the archaeon Thermoplasma acidophilum. Subsequent to proteasomal protein degradation, tricorn generates small peptides, which are cleaved by F1 to yield single amino acids. We have solved the crystal structure of F1 with multiwavelength anomalous dispersion (MAD) phasing at 1.8 Angstrom resolution. In addition to the conserved catalytic domain, the structure reveals a chiefly a-helical domain capping the catalytic triad. Thus, the active site is accessible only through a narrow opening from the protein surface. Two structures with molecules bound to the active serine, including the inhibitor phenylalanyl chloromethylketone, elucidate the N-terminal recognition of substrates and the catalytic activation switch mechanism of F1. The cap domain mainly confers the specificity for hydrophobic side chains by a novel cavity system, which, analogously to the tricorn protease, guides substrates to the buried active site and products away from it. Finally, the structure of F1 suggests a possible functional complex with tricorn that allows efficient processive degradation to free amino acids for cellular recycling.

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Language(s): eng - English
 Dates: 2002-10-15
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: eDoc: 41770
ISI: 000178802100004
 Degree: -

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Title: EMBO Journal
  Alternative Title : Embo J.
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: -
Pages: - Volume / Issue: 21 (20) Sequence Number: - Start / End Page: 5343 - 5352 Identifier: ISSN: 0261-4189