1btu: Difference between revisions

Revision as of 12:59, 21 February 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 with , and as ligands. Active as Pancreatic elastase, with EC number 3.4.21.36 Known structural/functional Site: . 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 Thu Feb 21 11:59:03 2008

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

@@ Line 4: / Line 4: @@
 ==Overview==
-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.
+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 Structure==
@@ Line 14: / Line 14: @@
 [[Category: Single protein]]
 [[Category: Sus scrofa]]
-[[Category: Clifton, I.J.]]
+[[Category: Clifton, I J.]]
-[[Category: Schofield, C.J.]]
+[[Category: Schofield, C J.]]
-[[Category: Wilmouth, R.C.]]
+[[Category: Wilmouth, R C.]]
 [[Category: 2BL]]
 [[Category: CA]]
@@ Line 23: / Line 23: @@
 [[Category: serine proteinase]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Feb  3 09:33:59 2008''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 11:59:03 2008''