1tve: Difference between revisions
From Proteopedia
Jump to navigationJump to search
New page: left|200px<br /><applet load="1tve" size="450" color="white" frame="true" align="right" spinBox="true" caption="1tve, resolution 3.00Å" /> '''Homoserine Dehydroge... |
No edit summary |
||
| Line 1: | Line 1: | ||
[[Image:1tve.gif|left|200px]]<br /><applet load="1tve" size=" | [[Image:1tve.gif|left|200px]]<br /><applet load="1tve" size="350" color="white" frame="true" align="right" spinBox="true" | ||
caption="1tve, resolution 3.00Å" /> | caption="1tve, resolution 3.00Å" /> | ||
'''Homoserine Dehydrogenase in complex with 4-(4-hydroxy-3-isopropylphenylthio)-2-isopropylphenol'''<br /> | '''Homoserine Dehydrogenase in complex with 4-(4-hydroxy-3-isopropylphenylthio)-2-isopropylphenol'''<br /> | ||
==Overview== | ==Overview== | ||
A relatively unexploited potential target for antimicrobial agents is the | 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== | ==About this Structure== | ||
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 178 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:// | 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]. | ||
==Reference== | ==Reference== | ||
| Line 14: | Line 14: | ||
[[Category: Saccharomyces cerevisiae]] | [[Category: Saccharomyces cerevisiae]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Berghuis, A | [[Category: Berghuis, A M.]] | ||
[[Category: Capone, C.]] | [[Category: Capone, C.]] | ||
[[Category: Chee, G | [[Category: Chee, G L.]] | ||
[[Category: Ejim, L.]] | [[Category: Ejim, L.]] | ||
[[Category: Jenkins, S.]] | [[Category: Jenkins, S.]] | ||
[[Category: Mirza, I | [[Category: Mirza, I A.]] | ||
[[Category: Nazi, I.]] | [[Category: Nazi, I.]] | ||
[[Category: Wright, G | [[Category: Wright, G D.]] | ||
[[Category: 178]] | [[Category: 178]] | ||
[[Category: antifungal; small molecule screening; amino acid biosynthesis]] | [[Category: antifungal; small molecule screening; amino acid biosynthesis]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:17:45 2008'' | ||
