1qr3
From Proteopedia
OCA (Talk | contribs)
(New page: 200px<br /><applet load="1qr3" size="450" color="white" frame="true" align="right" spinBox="true" caption="1qr3, resolution 1.6Å" /> '''STRUCTURE OF PORCINE ...)
Next diff →
Revision as of 22:47, 20 November 2007
|
STRUCTURE OF PORCINE PANCREATIC ELASTASE IN COMPLEX WITH FR901277, A NOVEL MACROCYCLIC INHIBITOR OF ELASTASES AT 1.6 ANGSTROM RESOLUTION
Overview
Human leukocyte elastase (HLE) is a serine protease that contributes to, tissue destruction in various disease states-for example, in emphysema., FR901277 is a natural product isolated from the culture filtrate of, Streptomyces resistomicificus and is a potent inhibitor of both HLE and, porcine pancreatic elastase (PPE). FR901277 consists of four normal amino, acids and three unusual amino acids, and is a unique bicyclic peptide, compound. The crystal structure of PPE complexed with FR901277 has been, determined at 1.6 A resolution. The Ogamma atom of Ser-195 in PPE did not, form a covalent bond with FR901277, but formed a hydrogen bond with the, Nvarepsilon atom of His-57. On the other hand, the portion from L-Orn(1), through dehydroxyThr(3) in FR901277 formed an antiparallel beta-sheet, structure with the backbone of the active site in PPE. The S4 through S2', binding subsites in PPE were all occupied by the hydrophobic side chains, of the inhibitor molecule. Especially, the ethylidene moiety of FR901277, occupied the S1 specific pocket, indicating a CH/pi interaction. In, addition, the isopropyl side chain of L-Val(7) was located at the enzyme, surface between the S2 and S1' pockets with several van der Waals, contacts. However, the amino acid (4) residue was not involved in a, significant interaction with PPE. Comparison of inhibitor structures in, different environments showed that FR901277 has a highly rigid bicyclic, framework; however, it can slightly change its conformation according to, the circumstances. The binding mode of FR901277 at the active site of PPE, was directly applicable to that in HLE, after consideration of induced, fit. The structure of the PPE-FR901277 complex provided much information, regarding potential sites for modification of the physicochemical, properties of FR901277.
About this Structure
1QR3 is a Single protein structure of sequence from Streptomyces resistomycificus and Sus scrofa with CA and SO4 as ligands. Active as Pancreatic elastase, with EC number 3.4.21.36 Full crystallographic information is available from OCA.
Reference
Structure of porcine pancreatic elastase complexed with FR901277, a novel macrocyclic inhibitor of elastases, at 1.6 A resolution., Nakanishi I, Kinoshita T, Sato A, Tada T, Biopolymers. 2000 Apr 15;53(5):434-45. PMID:10738204
Page seeded by OCA on Wed Nov 21 00:54:34 2007
