1scn
From Proteopedia
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|PDB= 1scn |SIZE=350|CAPTION= <scene name='initialview01'>1scn</scene>, resolution 1.9Å | |PDB= 1scn |SIZE=350|CAPTION= <scene name='initialview01'>1scn</scene>, resolution 1.9Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene> | + | |LIGAND= <scene name='pdbligand=APE:(1-AMINO-2-PHENYL-ETHYL)-CARBAMIC+ACID'>APE</scene>, <scene name='pdbligand=BOC:TERT-BUTYL+HYDROGEN+CARBONATE'>BOC</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene> |
| - | |ACTIVITY= [http://en.wikipedia.org/wiki/Subtilisin Subtilisin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.62 3.4.21.62] | + | |ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Subtilisin Subtilisin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.62 3.4.21.62] </span> |
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY= | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1scn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1scn OCA], [http://www.ebi.ac.uk/pdbsum/1scn PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1scn RCSB]</span> | ||
}} | }} | ||
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[[Category: Ringe, D.]] | [[Category: Ringe, D.]] | ||
[[Category: Steinmetz, A C.U.]] | [[Category: Steinmetz, A C.U.]] | ||
| - | [[Category: CA]] | ||
| - | [[Category: NA]] | ||
[[Category: complex(serine proteinase/inhibitor)]] | [[Category: complex(serine proteinase/inhibitor)]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 23:40:15 2008'' |
Revision as of 20:40, 30 March 2008
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| , resolution 1.9Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , , , | ||||||
| Activity: | Subtilisin, with EC number 3.4.21.62 | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
INACTIVATION OF SUBTILISIN CARLSBERG BY N-(TERT-BUTOXYCARBONYL-ALANYL-PROLYL-PHENYLALANYL)-O-BENZOYL HYDROXYLAMINE: FORMATION OF COVALENT ENZYME-INHIBITOR LINKAGE IN THE FORM OF A CARBAMATE DERIVATIVE
Overview
The mechanism of inactivation of serine proteases by N-peptidyl-O-aroylhydroxylamines was studied by X-ray crystallography. Cocrystals of subtilisin Carlsberg inactivated with N-((tert-butoxycarbonyl)alanylprolylphenylalanyl)-O-nitrobenzoy lhydroxylamine were grown, and diffraction data to 1.8-A resolution were obtained. The resulting electron density maps clearly reveal that the gamma-oxygen of the catalytic serine forms a carbamate derivative with the inhibitor. The peptide part of the inhibitor does not form the usual antiparallel beta-sheet in the P binding cleft but protrudes out of the active site and is stabilized by a network of water molecules. These results, combined with kinetic characterization reported previously [Demuth, H.-U., Schoenlein, C., & Barth, A. (1989b) Biochim. Biophys. Acta 996, 19-22; Schmidt, C., Schmidt, R., & Demuth, H.-U. (1990) Peptides (Giralt, E., & Andreu, D., Eds.) ESCOM Science Publishers B.V., Amsterdam] support the existence of at least one intermediate between the formation of the Michaelis complex and the final product. We suggest a mechanism for the inactivation of subtilisin Carlsberg by N-((tert-butoxycarbonyl)alanylprolylphenylalanyl)-O-benzoylhydr oxylamine whereby a negatively charged Michaelis complex undergoes a Lossen rearrangement giving rise to an isocyanate intermediate that reacts with the side chain of the active site serine.
About this Structure
1SCN is a Single protein structure of sequence from [1]. Full crystallographic information is available from OCA.
Reference
Inactivation of subtilisin Carlsberg by N-((tert-butoxycarbonyl)alanylprolylphenylalanyl)-O-benzoylhydroxyl- amine: formation of a covalent enzyme-inhibitor linkage in the form of a carbamate derivative., Steinmetz AC, Demuth HU, Ringe D, Biochemistry. 1994 Aug 30;33(34):10535-44. PMID:8068694
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