2i7u
From Proteopedia
| Line 1: | Line 1: | ||
[[Image:2i7u.jpg|left|200px]] | [[Image:2i7u.jpg|left|200px]] | ||
| - | + | <!-- | |
| - | + | The line below this paragraph, containing "STRUCTURE_2i7u", 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_2i7u| PDB=2i7u | SCENE= }} | |
| - | + | ||
| - | + | ||
| - | }} | + | |
'''Structural and Dynamical Analysis of a Four-Alpha-Helix Bundle with Designed Anesthetic Binding Pockets''' | '''Structural and Dynamical Analysis of a Four-Alpha-Helix Bundle with Designed Anesthetic Binding Pockets''' | ||
| Line 19: | Line 16: | ||
==About this Structure== | ==About this Structure== | ||
| - | + | Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2I7U OCA]. | |
==Reference== | ==Reference== | ||
Four-{alpha}-Helix Bundle with Designed Anesthetic Binding Pockets I: Structural and Dynamical Analyses., Ma D, Brandon NR, Cui T, Bondarenko V, Canlas C, Johansson JS, Tang P, Xu Y, Biophys J. 2008 Feb 29;. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/18310240 18310240] | Four-{alpha}-Helix Bundle with Designed Anesthetic Binding Pockets I: Structural and Dynamical Analyses., Ma D, Brandon NR, Cui T, Bondarenko V, Canlas C, Johansson JS, Tang P, Xu Y, Biophys J. 2008 Feb 29;. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/18310240 18310240] | ||
| - | [[Category: Protein complex]] | ||
[[Category: Bondarenko, V.]] | [[Category: Bondarenko, V.]] | ||
[[Category: Brandon, N R.]] | [[Category: Brandon, N R.]] | ||
| Line 32: | Line 28: | ||
[[Category: Tang, P.]] | [[Category: Tang, P.]] | ||
[[Category: Xu, Y.]] | [[Category: Xu, Y.]] | ||
| - | [[Category: | + | [[Category: Alpha helix]] |
| - | [[Category: | + | [[Category: Anesthetic binding]] |
| - | [[Category: | + | [[Category: De novo protein/ligand binding protein complex]] |
| - | [[Category: | + | [[Category: Four-alpha-helix bundle]] |
| - | [[Category: | + | [[Category: Homo dimer]] |
| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 07:11:20 2008'' | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | |
Revision as of 04:11, 4 May 2008
Structural and Dynamical Analysis of a Four-Alpha-Helix Bundle with Designed Anesthetic Binding Pockets
Overview
The four-alpha-helix bundle mimics the transmembrane domain of the Cys-loop receptor family believed to be the protein target for general anesthetics. Using high resolution NMR, we solved the structure (PDB ID: 2I7U) of a prototypical dimeric four-alpha-helix bundle, (Aalpha2-L1M/L38M)2, with designed specific binding pockets for volatile anesthetics. Two monomers of the helix-turn-helix motif form an anti-parallel dimer as originally designed, but the high-resolution structure exhibits an asymmetric quaternary arrangement of the four helices. The two helices from the N-terminus to the linker (helices 1 and 1') are associated with each other in the dimer by the side-chain ring stacking of F12 and W15 along the long hydrophobic core and by a nearly perfect stretch of hydrophobic interactions between the complementary pairs of L4, L11, L18, and L25, all of which are located at the heptad e position along the helix-helix dimer interface. In comparison, the axes of the two helices from the linker to the C-terminus (helices 2 and 2') are wider apart from each other, creating a lateral access pathway around K47 from the aqueous phase to the center of the designed hydrophobic core. The site of the L38M mutation, which was previously shown to increase the halothane binding affinity by ~3.5 fold, is not part of the hydrophobic core presumably involved in the anesthetic binding but shows an elevated transverse relaxation (R2) rate. Qualitative analysis of the protein dynamics by reduced spectral density mapping revealed exchange contributions to the relaxation at many residues in the helices. This was confirmed by the quantitative analysis using the Model-Free approach and by the NMR relaxation dispersion measurements. The NMR structures and Autodock analysis suggest that the pocket with most favorable amphipathic property for anesthetic binding is located between the W15 side chains at the center of the dimeric hydrophobic core, with the possibility of two additional minor binding sites between the F12 and F52 ring stacks of each monomer. The high-resolution structure of the designed anesthetic-binding protein offers unprecedented atomistic details about possible sites for anesthetic-protein interactions that are essential to the understanding of molecular mechanisms of general anesthesia.
About this Structure
Full crystallographic information is available from OCA.
Reference
Four-{alpha}-Helix Bundle with Designed Anesthetic Binding Pockets I: Structural and Dynamical Analyses., Ma D, Brandon NR, Cui T, Bondarenko V, Canlas C, Johansson JS, Tang P, Xu Y, Biophys J. 2008 Feb 29;. PMID:18310240 Page seeded by OCA on Sun May 4 07:11:20 2008
