1btu: Difference between revisions

Revision as of 11:57, 2 May 2008

PORCINE PANCREATIC ELASTASE COMPLEXED WITH (3S, 4R)-1-TOLUENESULPHONYL-3-ETHYL-AZETIDIN-2-ONE-4-CARBOXYLIC ACID

OverviewOverview

beta-Lactam inhibitors of transpeptidase enzymes involved in cell wall biosynthesis remain among the most important therapeutic agents in clinical use. beta-Lactams have more recently been developed as inhibitors of serine proteases including elastase. All therapeutically useful beta-lactam inhibitors operate via mechanisms resulting in the formation of hydrolytically stable acyl-enzyme complexes. Presently, it is difficult to predict which beta-lactams will form stable acyl-enzyme complexes with serine enzymes. Further, the factors that result in the seemingly special nature of beta-lactams versus other acylating agents are unclear-if indeed they exist. Here we present the 1.6 A resolution crystal structure of a stable acyl-enzyme complex formed between porcine pancreatic elastase and a representative monocyclic beta-lactam, which forms a simple acyl-enzyme. The structure shows that the ester carbonyl is not located within the oxyanion hole and the "hydrolytic" water is displaced. Combined with additional kinetic and mass spectrometric data, the structure allows the rationalization of the low degree of hydrolytic lability observed for the beta-lactam-derived acyl-enzyme complex.

About this StructureAbout this Structure

1BTU is a Single protein structure of sequence from Sus scrofa. Full crystallographic information is available from OCA.

ReferenceReference

Inhibition of elastase by N-sulfonylaryl beta-lactams: anatomy of a stable acyl-enzyme complex., Wilmouth RC, Westwood NJ, Anderson K, Brownlee W, Claridge TD, Clifton IJ, Pritchard GJ, Aplin RT, Schofield CJ, Biochemistry. 1998 Dec 15;37(50):17506-13. PMID:9860865 Page seeded by OCA on Fri May 2 11:56:59 2008

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OCA

@@ Line 1: / Line 1: @@
 [[Image:1btu.gif|left|200px]]
- {{Structure
+<!--
-|PDB= 1btu |SIZE=350|CAPTION= <scene name='initialview01'>1btu</scene>, resolution 1.6&Aring;
+The line below this paragraph, containing "STRUCTURE_1btu", creates the "Structure Box" on the page.
-|SITE= <scene name='pdbsite=CAT:Catalytic+Site'>CAT</scene>
+You may change the PDB parameter (which sets the PDB file loaded into the applet)
-|LIGAND= <scene name='pdbligand=2BL:(3S,+4R)-1-TOLUENESULPHONYL-3-ETHYL-AZETIDIN-2-ONE-4-CARBOXYLIC+ACID'>2BL</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>
+or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-|ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Pancreatic_elastase Pancreatic elastase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.36 3.4.21.36] </span>
+or leave the SCENE parameter empty for the default display.
-|GENE=
+-->
-|DOMAIN=
+{{STRUCTURE_1btu|  PDB=1btu  |  SCENE=  }}
-|RELATEDENTRY=
-|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1btu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1btu OCA], [http://www.ebi.ac.uk/pdbsum/1btu PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1btu RCSB]</span>
-}}
 '''PORCINE PANCREATIC ELASTASE COMPLEXED WITH (3S, 4R)-1-TOLUENESULPHONYL-3-ETHYL-AZETIDIN-2-ONE-4-CARBOXYLIC ACID'''
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 [[Category: Schofield, C J.]]
 [[Category: Wilmouth, R C.]]
-[[Category: hydrolase]]
+[[Category: Hydrolase]]
-[[Category: serine proteinase]]
+[[Category: Serine proteinase]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May  2 11:56:59 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 19:08:11 2008''