1qr3
From Proteopedia
| Line 1: | Line 1: | ||
[[Image:1qr3.jpg|left|200px]] | [[Image:1qr3.jpg|left|200px]] | ||
| - | + | <!-- | |
| - | + | The line below this paragraph, containing "STRUCTURE_1qr3", creates the "Structure Box" on the page. | |
| - | + | You may change the PDB parameter (which sets the PDB file loaded into the applet) | |
| - | + | or the SCENE parameter (which sets the initial scene displayed when the page is loaded), | |
| - | + | or leave the SCENE parameter empty for the default display. | |
| - | | | + | --> |
| - | | | + | {{STRUCTURE_1qr3| PDB=1qr3 | SCENE= }} |
| - | + | ||
| - | + | ||
| - | }} | + | |
'''STRUCTURE OF PORCINE PANCREATIC ELASTASE IN COMPLEX WITH FR901277, A NOVEL MACROCYCLIC INHIBITOR OF ELASTASES AT 1.6 ANGSTROM RESOLUTION''' | '''STRUCTURE OF PORCINE PANCREATIC ELASTASE IN COMPLEX WITH FR901277, A NOVEL MACROCYCLIC INHIBITOR OF ELASTASES AT 1.6 ANGSTROM RESOLUTION''' | ||
| Line 31: | Line 28: | ||
[[Category: Sato, A.]] | [[Category: Sato, A.]] | ||
[[Category: Tada, T.]] | [[Category: Tada, T.]] | ||
| - | [[Category: | + | [[Category: Protease-inhibitor complex]] |
| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 06:36:31 2008'' | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | |
Revision as of 03:36, 3 May 2008
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. 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 Sat May 3 06:36:31 2008
