1btu: Difference between revisions
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==Overview== | ==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 ... | 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== | ==About this Structure== | ||
1BTU is a | 1BTU is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Sus_scrofa Sus scrofa] with CA, SO4 and 2BL as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Structure known Active Site: CAT. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1BTU OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: serine proteinase]] | [[Category: serine proteinase]] | ||
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 5 15:26:38 2007'' | ||
