1yz3

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Line 1: Line 1:
[[Image:1yz3.gif|left|200px]]
[[Image:1yz3.gif|left|200px]]
-
{{Structure
+
<!--
-
|PDB= 1yz3 |SIZE=350|CAPTION= <scene name='initialview01'>1yz3</scene>, resolution 2.40&Aring;
+
The line below this paragraph, containing "STRUCTURE_1yz3", 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=SAH:S-ADENOSYL-L-HOMOCYSTEINE'>SAH</scene>, <scene name='pdbligand=SKA:7,8-DICHLORO-1,2,3,4-TETRAHYDROISOQUINOLINE'>SKA</scene>
+
or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-
|ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Phenylethanolamine_N-methyltransferase Phenylethanolamine N-methyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.1.28 2.1.1.28] </span>
+
or leave the SCENE parameter empty for the default display.
-
|GENE=
+
-->
-
|DOMAIN=
+
{{STRUCTURE_1yz3| PDB=1yz3 | SCENE= }}
-
|RELATEDENTRY=[[1hnn|1HNN]], [[1n7i|1N7I]], [[1n7j|1N7J]]
+
-
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1yz3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1yz3 OCA], [http://www.ebi.ac.uk/pdbsum/1yz3 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1yz3 RCSB]</span>
+
-
}}
+
'''Structure of human pnmt complexed with cofactor product adohcy and inhibitor SK&F 64139'''
'''Structure of human pnmt complexed with cofactor product adohcy and inhibitor SK&F 64139'''
Line 32: Line 29:
[[Category: McLeish, M J.]]
[[Category: McLeish, M J.]]
[[Category: Wu, Q.]]
[[Category: Wu, Q.]]
-
[[Category: enzyme]]
+
[[Category: Enzyme]]
-
[[Category: inhibitor complex]]
+
[[Category: Inhibitor complex]]
-
[[Category: product]]
+
[[Category: Product]]
-
 
+
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 16:59:10 2008''
-
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 01:26:39 2008''
+

Revision as of 13:59, 3 May 2008

Image:1yz3.gif

Template:STRUCTURE 1yz3

Structure of human pnmt complexed with cofactor product adohcy and inhibitor SK&F 64139


Overview

The X-ray structure of human phenylethanolamine N-methyltransferase (hPNMT) complexed with its product, S-adenosyl-L-homocysteine (4), and the most potent inhibitor reported to date, SK&F 64139 (7), was used to identify the residues involved in inhibitor binding. Four of these residues, Val53, Lys57, Glu219 and Asp267, were replaced, in turn, with alanine. All variants had increased Km values for phenylethanolamine (10), but only D267A showed a noteworthy (20-fold) decrease in its kcat value. Both WT hPNMT and D267A had similar kcat values for a rigid analogue, anti-9-amino-6-(trifluoromethyl)benzonorbornene (12), suggesting that Asp267 plays an important role in positioning the substrate but does not participate directly in catalysis. The Ki values for the binding of inhibitors such as 7 to the E219A and D267A variants increased by 2-3 orders of magnitude. Further, the inhibitors were shown to bind up to 50-fold more tightly in the presence of S-adenosyl-L-methionine (3), suggesting that the binding of the latter brings about a conformational change in the enzyme.

About this Structure

1YZ3 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Structural, mutagenic, and kinetic analysis of the binding of substrates and inhibitors of human phenylethanolamine N-methyltransferase., Wu Q, Gee CL, Lin F, Tyndall JD, Martin JL, Grunewald GL, McLeish MJ, J Med Chem. 2005 Nov 17;48(23):7243-52. PMID:16279783 Page seeded by OCA on Sat May 3 16:59:10 2008

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1yz3"
Personal tools