1z6p
From Proteopedia
(New page: 200px<br /><applet load="1z6p" size="450" color="white" frame="true" align="right" spinBox="true" caption="1z6p, resolution 2.40Å" /> '''Glycogen phosphoryla...) |
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| - | [[Image:1z6p.jpg|left|200px]]<br /><applet load="1z6p" size=" | + | [[Image:1z6p.jpg|left|200px]]<br /><applet load="1z6p" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1z6p, resolution 2.40Å" /> | caption="1z6p, resolution 2.40Å" /> | ||
'''Glycogen phosphorylase AMP site inhibitor complex'''<br /> | '''Glycogen phosphorylase AMP site inhibitor complex'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Inhibition of glycogen phosphorylase (GP) has attracted considerable | + | Inhibition of glycogen phosphorylase (GP) has attracted considerable attention during the last five to 10 years as a means of treating the elevated hepatic glucose production seen in patients with type 2 diabetes. Several different GP inhibitors binding to various binding sites of the GP enzyme have been reported in the literature. In this paper we report on a novel class of compounds that have been identified as potent GP inhibitors. Their synthesis, mode of binding to the allosteric AMP site as well as in vitro data on GP inhibition are shown. The most potent inhibitor was found to be 4-[2,4-bis-(3-nitrobenzoylamino)phenoxy]phthalic acid (4j) with an IC(50) value of 74 nM. This compound together with a closely related analogue was further characterized by enzyme kinetics and in primary rat hepatocytes. |
==About this Structure== | ==About this Structure== | ||
| - | 1Z6P is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Oryctolagus_cuniculus Oryctolagus cuniculus] with 194 as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Phosphorylase Phosphorylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.1.1 2.4.1.1] Full crystallographic information is available from [http:// | + | 1Z6P is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Oryctolagus_cuniculus Oryctolagus cuniculus] with <scene name='pdbligand=194:'>194</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Phosphorylase Phosphorylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.1.1 2.4.1.1] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1Z6P OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Andersen, B.]] | [[Category: Andersen, B.]] | ||
| - | [[Category: Iversen, L | + | [[Category: Iversen, L F.]] |
[[Category: Kristiansen, M.]] | [[Category: Kristiansen, M.]] | ||
[[Category: Westergaard, N.]] | [[Category: Westergaard, N.]] | ||
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[[Category: glycogen metabolism; glycogen phosphorylase b; inhibition; allosteric]] | [[Category: glycogen metabolism; glycogen phosphorylase b; inhibition; allosteric]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:12:36 2008'' |
Revision as of 14:12, 21 February 2008
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Glycogen phosphorylase AMP site inhibitor complex
Overview
Inhibition of glycogen phosphorylase (GP) has attracted considerable attention during the last five to 10 years as a means of treating the elevated hepatic glucose production seen in patients with type 2 diabetes. Several different GP inhibitors binding to various binding sites of the GP enzyme have been reported in the literature. In this paper we report on a novel class of compounds that have been identified as potent GP inhibitors. Their synthesis, mode of binding to the allosteric AMP site as well as in vitro data on GP inhibition are shown. The most potent inhibitor was found to be 4-[2,4-bis-(3-nitrobenzoylamino)phenoxy]phthalic acid (4j) with an IC(50) value of 74 nM. This compound together with a closely related analogue was further characterized by enzyme kinetics and in primary rat hepatocytes.
About this Structure
1Z6P is a Single protein structure of sequence from Oryctolagus cuniculus with as ligand. Active as Phosphorylase, with EC number 2.4.1.1 Full crystallographic information is available from OCA.
Reference
Identification, synthesis, and characterization of new glycogen phosphorylase inhibitors binding to the allosteric AMP site., Kristiansen M, Andersen B, Iversen LF, Westergaard N, J Med Chem. 2004 Jul 1;47(14):3537-45. PMID:15214781
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