2h5c: Difference between revisions
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|PDB= 2h5c |SIZE=350|CAPTION= <scene name='initialview01'>2h5c</scene>, resolution 0.82Å | |PDB= 2h5c |SIZE=350|CAPTION= <scene name='initialview01'>2h5c</scene>, resolution 0.82Å | ||
|SITE= | |SITE= | ||
|LIGAND= <scene name='pdbligand= | |LIGAND= <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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] | |ACTIVITY= <span class='plainlinks'>[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] </span> | ||
|GENE= | |GENE= | ||
|DOMAIN= | |||
|RELATEDENTRY=[[1ssx|1SSX]], [[1tal|1TAL]], [[2ull|2ULL]], [[1qrx|1QRX]] | |||
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2h5c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2h5c OCA], [http://www.ebi.ac.uk/pdbsum/2h5c PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2h5c RCSB]</span> | |||
}} | }} | ||
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[[Category: Daugherty, M D.]] | [[Category: Daugherty, M D.]] | ||
[[Category: Fuhrmann, C N.]] | [[Category: Fuhrmann, C N.]] | ||
[[Category: a-lytic protease]] | [[Category: a-lytic protease]] | ||
[[Category: acylation transition state]] | [[Category: acylation transition state]] | ||
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[[Category: ultra-high resolution]] | [[Category: ultra-high resolution]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 03:25:41 2008'' | ||
Revision as of 03:25, 31 March 2008
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| , resolution 0.82Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , | ||||||
| Activity: | Alpha-lytic endopeptidase, with EC number 3.4.21.12 | ||||||
| Related: | 1SSX, 1TAL, 2ULL, 1QRX
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
0.82A resolution crystal structure of alpha-lytic protease at pH 5
OverviewOverview
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 StructureAbout this Structure
2H5C is a Single protein structure of sequence from Lysobacter enzymogenes. Full crystallographic information is available from OCA.
ReferenceReference
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
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