This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.
Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.
2h5d
From Proteopedia
| Line 1: | Line 1: | ||
| - | [[Image:2h5d.jpg|left|200px]] | + | [[Image:2h5d.jpg|left|200px]] |
| - | + | ||
| - | '''0.9A resolution crystal structure of alpha-lytic protease complexed with a transition state analogue, MeOSuc-Ala-Ala-Pro-Val boronic acid''' | + | {{Structure |
| + | |PDB= 2h5d |SIZE=350|CAPTION= <scene name='initialview01'>2h5d</scene>, resolution 0.90Å | ||
| + | |SITE= | ||
| + | |LIGAND= <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene> and <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene> | ||
| + | |ACTIVITY= [http://en.wikipedia.org/wiki/Alpha-lytic_endopeptidase Alpha-lytic endopeptidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.12 3.4.21.12] | ||
| + | |GENE= | ||
| + | }} | ||
| + | |||
| + | '''0.9A resolution crystal structure of alpha-lytic protease complexed with a transition state analogue, MeOSuc-Ala-Ala-Pro-Val boronic acid''' | ||
| + | |||
==Overview== | ==Overview== | ||
| Line 7: | Line 16: | ||
==About this Structure== | ==About this Structure== | ||
| - | 2H5D is a [ | + | 2H5D is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Lysobacter_enzymogenes Lysobacter enzymogenes]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2H5D OCA]. |
==Reference== | ==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:[http:// | + | 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:[http://www.ncbi.nlm.nih.gov/pubmed/16834383 16834383] |
[[Category: Alpha-lytic endopeptidase]] | [[Category: Alpha-lytic endopeptidase]] | ||
[[Category: Lysobacter enzymogenes]] | [[Category: Lysobacter enzymogenes]] | ||
| Line 27: | Line 36: | ||
[[Category: ultra-high resolution]] | [[Category: ultra-high resolution]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 17:12:49 2008'' |
Revision as of 15:12, 20 March 2008
| |||||||
| , resolution 0.90Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | and | ||||||
| Activity: | Alpha-lytic endopeptidase, with EC number 3.4.21.12 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
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.
About this Structure
2H5D 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 Thu Mar 20 17:12:49 2008
