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[[Image:1scn.jpg|left|200px]]
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{{STRUCTURE_1scn|  PDB=1scn  |  SCENE=  }}
'''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'''


==INACTIVATION OF SUBTILISIN CARLSBERG BY N-(TERT-BUTOXYCARBONYL-ALANYL-PROLYL-PHENYLALANYL)-O-BENZOL HYDROXYLAMINE: FORMATION OF COVALENT ENZYME-INHIBITOR LINKAGE IN THE FORM OF A CARBAMATE DERIVATIVE==
<StructureSection load='1scn' size='340' side='right'caption='[[1scn]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1scn]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Bacillus_licheniformis Bacillus licheniformis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1SCN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1SCN FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.9&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0EF:N-(TERT-BUTOXYCARBONYL)-L-ALANYL-N-[(1R)-1-(CARBOXYAMINO)-2-PHENYLETHYL]-L-PROLINAMIDE'>0EF</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1scn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1scn OCA], [https://pdbe.org/1scn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1scn RCSB], [https://www.ebi.ac.uk/pdbsum/1scn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1scn ProSAT]</span></td></tr>
</table>
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/sc/1scn_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1scn ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
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., &amp; Barth, A. (1989b) Biochim. Biophys. Acta 996, 19-22; Schmidt, C., Schmidt, R., &amp; Demuth, H.-U. (1990) Peptides (Giralt, E., &amp; 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.


==Overview==
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<ref>PMID:8068694</ref>
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., &amp; Barth, A. (1989b) Biochim. Biophys. Acta 996, 19-22; Schmidt, C., Schmidt, R., &amp; Demuth, H.-U. (1990) Peptides (Giralt, E., &amp; 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==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
1SCN is a [[Single protein]] structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1SCN OCA].
</div>
<div class="pdbe-citations 1scn" style="background-color:#fffaf0;"></div>


==Reference==
==See Also==
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:[http://www.ncbi.nlm.nih.gov/pubmed/8068694 8068694]
*[[Subtilisin 3D structures|Subtilisin 3D structures]]
[[Category: Single protein]]
== References ==
[[Category: Subtilisin]]
<references/>
[[Category: Demuth, H U.]]
__TOC__
[[Category: Ringe, D.]]
</StructureSection>
[[Category: Steinmetz, A C.U.]]
[[Category: Bacillus licheniformis]]
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May  3 08:33:02 2008''
[[Category: Large Structures]]
[[Category: Demuth H-U]]
[[Category: Ringe D]]
[[Category: Steinmetz ACU]]

Latest revision as of 00:28, 21 November 2024

INACTIVATION OF SUBTILISIN CARLSBERG BY N-(TERT-BUTOXYCARBONYL-ALANYL-PROLYL-PHENYLALANYL)-O-BENZOL HYDROXYLAMINE: FORMATION OF COVALENT ENZYME-INHIBITOR LINKAGE IN THE FORM OF A CARBAMATE DERIVATIVE

1scn, resolution 1.90Å

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