2h5c
From Proteopedia
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| - | | | + | {{STRUCTURE_2h5c| PDB=2h5c | SCENE= }} |
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'''0.82A resolution crystal structure of alpha-lytic protease at pH 5''' | '''0.82A resolution crystal structure of alpha-lytic protease at pH 5''' | ||
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[[Category: Daugherty, M D.]] | [[Category: Daugherty, M D.]] | ||
[[Category: Fuhrmann, C N.]] | [[Category: Fuhrmann, C N.]] | ||
| - | [[Category: | + | [[Category: A-lytic protease]] |
| - | [[Category: | + | [[Category: Acylation transition state]] |
| - | [[Category: | + | [[Category: Catalysis]] |
| - | [[Category: | + | [[Category: Packing distortion]] |
| - | [[Category: | + | [[Category: Protein folding]] |
| - | [[Category: | + | [[Category: Protein stability]] |
| - | [[Category: | + | [[Category: Serine protease]] |
| - | [[Category: | + | [[Category: Ultra-high resolution]] |
| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 05:53:04 2008'' | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | |
Revision as of 02:53, 4 May 2008
0.82A resolution crystal structure of alpha-lytic protease at pH 5
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.
About this Structure
2H5C is a Single protein structure of sequence from Lysobacter enzymogenes. Full crystallographic information is available from OCA.
Reference
Subangstrom crystallography reveals that short ionic hydrogen bonds, and not a His-Asp low-barrier hydrogen bond, stabilize the transition state in serine protease catalysis., Fuhrmann CN, Daugherty MD, Agard DA, J Am Chem Soc. 2006 Jul 19;128(28):9086-102. PMID:16834383 Page seeded by OCA on Sun May 4 05:53:04 2008
