|
|
| Line 1: |
Line 1: |
| [[Image:2h5d.jpg|left|200px]] | | {{Seed}} |
| | [[Image:2h5d.png|left|200px]] |
|
| |
|
| <!-- | | <!-- |
| Line 9: |
Line 10: |
| {{STRUCTURE_2h5d| PDB=2h5d | SCENE= }} | | {{STRUCTURE_2h5d| PDB=2h5d | SCENE= }} |
|
| |
|
| '''0.9A resolution crystal structure of alpha-lytic protease complexed with a transition state analogue, MeOSuc-Ala-Ala-Pro-Val boronic acid'''
| | ===0.9A resolution crystal structure of alpha-lytic protease complexed with a transition state analogue, MeOSuc-Ala-Ala-Pro-Val boronic acid=== |
|
| |
|
|
| |
|
| ==Overview==
| | <!-- |
| To address questions regarding the mechanism of serine protease catalysis, we have solved two X-ray crystal structures of alpha-lytic protease (alphaLP) that mimic aspects of the transition states: alphaLP at pH 5 (0.82 A resolution) and alphaLP bound to the peptidyl boronic acid inhibitor, MeOSuc-Ala-Ala-Pro-boroVal (0.90 A resolution). Based on these structures, there is no evidence of, or requirement for, histidine-flipping during the acylation step of the reaction. Rather, our data suggests that upon protonation of His57, Ser195 undergoes a conformational change that destabilizes the His57-Ser195 hydrogen bond, preventing the back-reaction. In both structures the His57-Asp102 hydrogen bond in the catalytic triad is a normal ionic hydrogen bond, and not a low-barrier hydrogen bond (LBHB) as previously hypothesized. We propose that the enzyme has evolved a network of relatively short hydrogen bonds that collectively stabilize the transition states. In particular, a short ionic hydrogen bond (SIHB) between His57 Nepsilon2 and the substrate's leaving group may promote forward progression of the TI1-to-acylenzyme reaction. We provide experimental evidence that refutes use of either a short donor-acceptor distance or a downfield 1H chemical shift as sole indicators of a LBHB.
| | The line below this paragraph, {{ABSTRACT_PUBMED_16834383}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 16834383 is the PubMed ID number. |
| | --> |
| | {{ABSTRACT_PUBMED_16834383}} |
|
| |
|
| ==About this Structure== | | ==About this Structure== |
| Line 33: |
Line 37: |
| [[Category: Serine protease]] | | [[Category: Serine protease]] |
| [[Category: Ultra-high resolution]] | | [[Category: Ultra-high resolution]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 05:53:15 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 19:41:20 2008'' |
