2o7o

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Line 1: Line 1:
[[Image:2o7o.gif|left|200px]]
[[Image:2o7o.gif|left|200px]]
-
{{Structure
+
<!--
-
|PDB= 2o7o |SIZE=350|CAPTION= <scene name='initialview01'>2o7o</scene>, resolution 1.89&Aring;
+
The line below this paragraph, containing "STRUCTURE_2o7o", creates the "Structure Box" on the page.
-
|SITE=
+
You may change the PDB parameter (which sets the PDB file loaded into the applet)
-
|LIGAND= <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=DXT:(4S,4AR,5S,5AR,6R,12AS)-4-(DIMETHYLAMINO)-3,5,10,12,12A-PENTAHYDROXY-6-METHYL-1,11-DIOXO-1,4,4A,5,5A,6,11,12A-OCTAHYDROTETRACENE-2-CARBOXAMIDE'>DXT</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>
+
or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-
|ACTIVITY=
+
or leave the SCENE parameter empty for the default display.
-
|GENE=
+
-->
-
|DOMAIN=
+
{{STRUCTURE_2o7o| PDB=2o7o | SCENE= }}
-
|RELATEDENTRY=[[2tct|2TCT]]
+
-
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2o7o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2o7o OCA], [http://www.ebi.ac.uk/pdbsum/2o7o PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2o7o RCSB]</span>
+
-
}}
+
'''Crystal structure analysis of TetR(D) complex with doxycycline'''
'''Crystal structure analysis of TetR(D) complex with doxycycline'''
Line 28: Line 25:
[[Category: Hinrichs, W.]]
[[Category: Hinrichs, W.]]
[[Category: Proft, J.]]
[[Category: Proft, J.]]
-
[[Category: helix-turn-helix]]
+
[[Category: Helix-turn-helix]]
-
[[Category: metal coordination]]
+
[[Category: Metal coordination]]
-
 
+
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 10:25:28 2008''
-
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 04:13:53 2008''
+

Revision as of 07:25, 4 May 2008

Template:STRUCTURE 2o7o

Crystal structure analysis of TetR(D) complex with doxycycline


Overview

Resistance to the antibiotic tetracycline (Tc) is regulated by its binding as a Tc:Mg2+ complex to the Tet Repressor protein (TetR). Tc:TetR recognition is a complex problem, with the protein and ligand each having several possible conformations and protonation states, which are difficult to elucidate by experiment alone. We used a combination of free-energy simulations and crystallographic analysis to investigate the electrostatic interactions between protein and ligand and the possible role of induced fit in Tc binding. Tc in solution was described quantum mechanically, while Tc:TetR interactions were described by a recent, high-quality molecular-mechanics model. The orientations of the amide and imidazole groups were determined experimentally by a careful analysis of Debye-Waller factors in alternate crystallographic models. The agreement with experiment for these orientations suggested that the simulations and their more detailed, thermodynamic predictions were reliable. We found that the ligand prefers an extended, zwitterionic state both in solution and in complexation with the protein. Tc is thus preorganized for binding, while the protein combines lock-and-key behavior for regions close to the ligand's amide, enolate, and ammonium groups, with an induced fit for regions close to the Mg2+ ion. These insights and the modeling techniques employed should be of interest for engineering improved TetR ligands and improved TetR proteins for gene regulation, as well as for drug design.

About this Structure

2O7O is a Single protein structure of sequence from Escherichia coli. Full crystallographic information is available from OCA.

Reference

Protonation patterns in tetracycline:tet repressor recognition: simulations and experiments., Aleksandrov A, Proft J, Hinrichs W, Simonson T, Chembiochem. 2007 Apr 16;8(6):675-85. PMID:17361981 Page seeded by OCA on Sun May 4 10:25:28 2008

Proteopedia Page Contributors and Editors (what is this?)

OCA

Personal tools