|
|
| Line 1: |
Line 1: |
| [[Image:2f9p.gif|left|200px]] | | {{Seed}} |
| | [[Image:2f9p.png|left|200px]] |
|
| |
|
| <!-- | | <!-- |
| Line 9: |
Line 10: |
| {{STRUCTURE_2f9p| PDB=2f9p | SCENE= }} | | {{STRUCTURE_2f9p| PDB=2f9p | SCENE= }} |
|
| |
|
| '''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=== |
|
| |
|
|
| |
|
| ==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.
| | The line below this paragraph, {{ABSTRACT_PUBMED_16414069}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 16414069 is the PubMed ID number. |
| | --> |
| | {{ABSTRACT_PUBMED_16414069}} |
|
| |
|
| ==About this Structure== | | ==About this Structure== |
| Line 34: |
Line 38: |
| [[Category: Serine proteinase]] | | [[Category: Serine proteinase]] |
| [[Category: Trypsin-like]] | | [[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 Sun Jul 27 23:59:51 2008'' |
