2f9p
From Proteopedia
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| - | + | {{STRUCTURE_2f9p| PDB=2f9p | SCENE= }} | |
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'''Crystal Structure of the Recombinant Human Alpha I Tryptase Mutant D216G in Complex with Leupeptin''' | '''Crystal Structure of the Recombinant Human Alpha I Tryptase Mutant D216G in Complex with Leupeptin''' | ||
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[[Category: Selwood, T.]] | [[Category: Selwood, T.]] | ||
[[Category: Than, M E.]] | [[Category: Than, M E.]] | ||
| - | [[Category: | + | [[Category: Difucosylation]] |
| - | [[Category: | + | [[Category: Leupeptin]] |
| - | [[Category: | + | [[Category: Serine proteinase]] |
| - | [[Category: | + | [[Category: Trypsin-like]] |
| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 03:38:13 2008'' | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | |
Revision as of 00:38, 4 May 2008
Crystal Structure of the Recombinant Human Alpha I Tryptase Mutant D216G in Complex with Leupeptin
Overview
Tryptases alpha and beta are trypsin-like serine proteinases expressed in large amounts by mast cells. Beta-tryptase is a tetramer that has enzymatic activity, but requires heparin binding to maintain functional and structural stability, whereas alpha-tryptase has little, if any, enzymatic activity but is a stable tetramer in the absence of heparin. As shown previously, these differences can be mainly attributed to the different conformations of the 214-220 segment. Interestingly, the replacement of Asp216 by Gly, which is present in beta-tryptase, results in enzymatically active but less stable alpha-tryptase mutants. We have solved the crystal structures of both the single (D216G) and the double (K192Q/D216G) mutant forms of recombinant human alphaI-tryptase in complex with the peptide inhibitor leupeptin, as well as the structure of the non-inhibited single mutant. The inhibited mutants exhibited an open functional substrate binding site, while in the absence of an inhibitor, the open (beta-tryptase-like) and the closed (alpha-tryptase-like) conformations were present simultaneously. This shows that both forms are in a two-state equilibrium, which is influenced by the residues in the vicinity of the active site and by inhibitor/substrate binding. Novel insights regarding the observed stability differences as well as a potential proteolytic activity of wild-type alpha-tryptase, which may possess a cryptic active site, are discussed.
About this Structure
2F9P is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
X-ray structures of free and leupeptin-complexed human alphaI-tryptase mutants: indication for an alpha-->beta-tryptase transition., Rohr KB, Selwood T, Marquardt U, Huber R, Schechter NM, Bode W, Than ME, J Mol Biol. 2006 Mar 17;357(1):195-209. Epub 2005 Dec 28. PMID:16414069 Page seeded by OCA on Sun May 4 03:38:13 2008
