1tve

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[[Image:1tve.gif|left|200px]]<br /><applet load="1tve" size="350" color="white" frame="true" align="right" spinBox="true"
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[[Image:1tve.gif|left|200px]]
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caption="1tve, resolution 3.00&Aring;" />
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'''Homoserine Dehydrogenase in complex with 4-(4-hydroxy-3-isopropylphenylthio)-2-isopropylphenol'''<br />
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{{Structure
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|PDB= 1tve |SIZE=350|CAPTION= <scene name='initialview01'>1tve</scene>, resolution 3.00&Aring;
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|SITE=
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|LIGAND= <scene name='pdbligand=178:4-(4-HYDROXY-3-ISOPROPYLPHENYLTHIO)-2-ISOPROPYLPHENOL'>178</scene>
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|ACTIVITY= [http://en.wikipedia.org/wiki/Homoserine_dehydrogenase Homoserine dehydrogenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.3 1.1.1.3]
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|GENE= hom6 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=4932 Saccharomyces cerevisiae])
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}}
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'''Homoserine Dehydrogenase in complex with 4-(4-hydroxy-3-isopropylphenylthio)-2-isopropylphenol'''
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==Overview==
==Overview==
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==About this Structure==
==About this Structure==
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1TVE is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae] with <scene name='pdbligand=178:'>178</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Homoserine_dehydrogenase Homoserine dehydrogenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.3 1.1.1.3] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1TVE OCA].
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1TVE is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1TVE OCA].
==Reference==
==Reference==
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New phenolic inhibitors of yeast homoserine dehydrogenase., Ejim L, Mirza IA, Capone C, Nazi I, Jenkins S, Chee GL, Berghuis AM, Wright GD, Bioorg Med Chem. 2004 Jul 15;12(14):3825-30. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=15210149 15210149]
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New phenolic inhibitors of yeast homoserine dehydrogenase., Ejim L, Mirza IA, Capone C, Nazi I, Jenkins S, Chee GL, Berghuis AM, Wright GD, Bioorg Med Chem. 2004 Jul 15;12(14):3825-30. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/15210149 15210149]
[[Category: Homoserine dehydrogenase]]
[[Category: Homoserine dehydrogenase]]
[[Category: Saccharomyces cerevisiae]]
[[Category: Saccharomyces cerevisiae]]
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[[Category: antifungal; small molecule screening; amino acid biosynthesis]]
[[Category: antifungal; small molecule screening; amino acid biosynthesis]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:17:45 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 14:23:45 2008''

Revision as of 12:23, 20 March 2008


PDB ID 1tve

Drag the structure with the mouse to rotate
, resolution 3.00Å
Ligands:
Gene: hom6 (Saccharomyces cerevisiae)
Activity: Homoserine dehydrogenase, with EC number 1.1.1.3
Coordinates: save as pdb, mmCIF, xml



Homoserine Dehydrogenase in complex with 4-(4-hydroxy-3-isopropylphenylthio)-2-isopropylphenol


Overview

A relatively unexploited potential target for antimicrobial agents is the biosynthesis of essential amino acids. Homoserine dehydrogenase, which reduces aspartate semi-aldehyde to homoserine in a NAD(P)H-dependent reaction, is one such target that is required for the biosynthesis of Met, Thr, and Ile from Asp. We report a small molecule screen of yeast homoserine dehydrogenase that has identified a new class of phenolic inhibitors of this class of enzyme. X-ray crystal structural analysis of one of the inhibitors in complex with homoserine dehydrogenase reveals that these molecules bind in the amino acid binding region of the active site and that the phenolic hydroxyl group interacts specifically with the backbone amide of Gly175. These results provide the first nonamino acid inhibitors of this class of enzyme and have the potential to be exploited as leads in antifungal compound design.

About this Structure

1TVE is a Single protein structure of sequence from Saccharomyces cerevisiae. Full crystallographic information is available from OCA.

Reference

New phenolic inhibitors of yeast homoserine dehydrogenase., Ejim L, Mirza IA, Capone C, Nazi I, Jenkins S, Chee GL, Berghuis AM, Wright GD, Bioorg Med Chem. 2004 Jul 15;12(14):3825-30. PMID:15210149

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