1tlm

(Difference between revisions)

Categories: Homo sapiens | Single protein | Cody, V. | Luft, J. | Wojtczak, A.

Revision as of 07:06, 3 May 2008

STRUCTURAL ASPECTS OF INOTROPIC BIPYRIDINE BINDING: CRYSTAL STRUCTURE DETERMINATION TO 1.9 ANGSTROMS OF THE HUMAN SERUM TRANSTHYRETIN-MILRINONE COMPLEX

Overview

The crystal structure of human transthyretin (TTR) complexed with milrinone (2-methyl-5-cyano-3,4'-bipyridin-6(1H)-one), a positive inotropic cardiac agent, has been refined to R = 17.4% for 8-1.9-A resolution data. This report provides the first detailed description of protein interactions for an inotropic bipyridine agent which is an effective thyroid hormone binding competitor to transthyretin. Milrinone is bound along the 2-fold axis in the binding site with its substituted pyridone ring located deep within the channel of the two identical binding domains of the TTR tetramer. In this orientation the 5-cyano group occupies the same site as the 3'-iodine in the TTR complex with 3,3'-diiodothyronine (Wojtczak, A., Luft, J., and Cody, V. (1992) J. Biol. Chem. 267, 353-357), which is 3.5 A deeper in the channel than thyroxine (Blake, C. C. F., and Oately, S. J., (1977) Nature 268, 115-120). These structural results confirm computer modeling studies of milrinone structural homology with thyroxine and its TTR binding interactions and explain the effectiveness of milrinone competition for thyroxine binding to TTR. To understand the weaker binding affinity of the parent inotropic drug, amrinone (5-amino-3,4'-bipyridin-6(1H)-one), modeling studies of its TTR binding were carried out which indicate that the 5-amino group cannot participate in strong interactions with TTR and the lack of the 2-methyl further weakens amrinone binding.

About this Structure

1TLM is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Structural aspects of inotropic bipyridine binding. Crystal structure determination to 1.9 A of the human serum transthyretin-milrinone complex., Wojtczak A, Luft JR, Cody V, J Biol Chem. 1993 Mar 25;268(9):6202-6. PMID:8454595 Page seeded by OCA on Sat May 3 10:06:08 2008

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Retrieved from "http://52.214.119.220/wiki/index.php/1tlm"

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 [[Image:1tlm.jpg|left|200px]]
- {{Structure
+<!--
-|PDB= 1tlm |SIZE=350|CAPTION= <scene name='initialview01'>1tlm</scene>, resolution 1.9&Aring;
+The line below this paragraph, containing "STRUCTURE_1tlm", 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=MIL:MILRINONE'>MIL</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_1tlm|  PDB=1tlm  |  SCENE=  }}
-|RELATEDENTRY=
-|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1tlm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1tlm OCA], [http://www.ebi.ac.uk/pdbsum/1tlm PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1tlm RCSB]</span>
-}}
 '''STRUCTURAL ASPECTS OF INOTROPIC BIPYRIDINE BINDING: CRYSTAL STRUCTURE DETERMINATION TO 1.9 ANGSTROMS OF THE HUMAN SERUM TRANSTHYRETIN-MILRINONE COMPLEX'''
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 [[Category: Luft, J.]]
 [[Category: Wojtczak, A.]]
-[[Category: transport(thyroxine)]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May  3 10:06:08 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 23:57:50 2008''