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| - | [[Image:1n6d.gif|left|200px]] | + | {{Seed}} |
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| | {{STRUCTURE_1n6d| PDB=1n6d | SCENE= }} | | {{STRUCTURE_1n6d| PDB=1n6d | SCENE= }} |
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| - | '''Tricorn protease in complex with tetrapeptide chloromethyl ketone derivative'''
| + | ===Tricorn protease in complex with tetrapeptide chloromethyl ketone derivative=== |
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| - | ==Overview==
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| - | The proposed pathway and mechanism of substrate entry and product egress in the hexameric D3 symmetric tricorn protease from Thermoplasma acidophilum were explored by crystallographic studies of ligand complexes and by structure-based mutagenesis. Obstruction of the pore within the 7-bladed beta-propeller (beta7) domain by alkylation or oxidation of an engineered double cysteine mutant strongly decreased enzymatic activities. In line herewith, the crystal structure of the tricorn protease in complex with a trideca-peptide inhibitor modifying the catalytic Ser965 revealed part of the peptide trapped inside the channel of the beta7 domain. The cysteine mutation widening the lumen of the 6-bladed beta-propeller (beta6) domain enhanced catalytic activity, which was restored to normal values after its alkylation. A charge reversal mutant at the putative anchor site of the substrate C terminus, R131E-R132E, drastically reduced the proteolytic activity. The complex crystal structure of a peptide inhibitor with a diketo group at the cleavage site mapped the substrate recognition site and confirmed the role of Arg131-Arg132 as an anchor site. Our results strongly suggest the wider beta7 domain to serve as a selective filter and guide of the substrate to the sequestered active site, while the narrower beta6 domain routes the product to the surface. Moreover, we identified the role of Arg131-Arg132 in anchoring the substrate C terminus. | + | The line below this paragraph, {{ABSTRACT_PUBMED_12470958}}, adds the Publication Abstract to the page |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 12470958 is the PubMed ID number. |
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| | + | {{ABSTRACT_PUBMED_12470958}} |
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| | ==About this Structure== | | ==About this Structure== |
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| | [[Category: Propeller]] | | [[Category: Propeller]] |
| | [[Category: Tricorn protease]] | | [[Category: Tricorn protease]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 02:09:14 2008'' | + | |
| | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Jul 27 19:33:40 2008'' |
Revision as of 16:33, 27 July 2008
Template:STRUCTURE 1n6d
Tricorn protease in complex with tetrapeptide chloromethyl ketone derivative
Template:ABSTRACT PUBMED 12470958
About this Structure
1N6D is a Single protein structure of sequence from Thermoplasma acidophilum. Full crystallographic information is available from OCA.
Reference
Navigation inside a protease: substrate selection and product exit in the tricorn protease from Thermoplasma acidophilum., Kim JS, Groll M, Musiol HJ, Behrendt R, Kaiser M, Moroder L, Huber R, Brandstetter H, J Mol Biol. 2002 Dec 13;324(5):1041-50. PMID:12470958
Page seeded by OCA on Sun Jul 27 19:33:40 2008
