1q7g
From Proteopedia
| Line 1: | Line 1: | ||
| - | [[Image:1q7g.gif|left|200px]] | + | [[Image:1q7g.gif|left|200px]] |
| - | + | ||
| - | '''Homoserine Dehydrogenase in complex with suicide inhibitor complex NAD-5-hydroxy-4-Oxonorvaline''' | + | {{Structure |
| + | |PDB= 1q7g |SIZE=350|CAPTION= <scene name='initialview01'>1q7g</scene>, resolution 2.60Å | ||
| + | |SITE= | ||
| + | |LIGAND= <scene name='pdbligand=NA:SODIUM+ION'>NA</scene> and <scene name='pdbligand=NHO:NICOTINAMIDE-ADENINE-DINUCLEOTIDE-5-HYDROXY-4-OXONORVALINE'>NHO</scene> | ||
| + | |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] | ||
| + | |GENE= HOM6, YJR139C OR J2132 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=4932 Saccharomyces cerevisiae]) | ||
| + | }} | ||
| + | |||
| + | '''Homoserine Dehydrogenase in complex with suicide inhibitor complex NAD-5-hydroxy-4-Oxonorvaline''' | ||
| + | |||
==Overview== | ==Overview== | ||
| Line 7: | Line 16: | ||
==About this Structure== | ==About this Structure== | ||
| - | 1Q7G is a [ | + | 1Q7G 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=1Q7G OCA]. |
==Reference== | ==Reference== | ||
| - | Enzyme-assisted suicide: molecular basis for the antifungal activity of 5-hydroxy-4-oxonorvaline by potent inhibition of homoserine dehydrogenase., Jacques SL, Mirza IA, Ejim L, Koteva K, Hughes DW, Green K, Kinach R, Honek JF, Lai HK, Berghuis AM, Wright GD, Chem Biol. 2003 Oct;10(10):989-95. PMID:[http:// | + | Enzyme-assisted suicide: molecular basis for the antifungal activity of 5-hydroxy-4-oxonorvaline by potent inhibition of homoserine dehydrogenase., Jacques SL, Mirza IA, Ejim L, Koteva K, Hughes DW, Green K, Kinach R, Honek JF, Lai HK, Berghuis AM, Wright GD, Chem Biol. 2003 Oct;10(10):989-95. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/14583265 14583265] |
[[Category: Homoserine dehydrogenase]] | [[Category: Homoserine dehydrogenase]] | ||
[[Category: Saccharomyces cerevisiae]] | [[Category: Saccharomyces cerevisiae]] | ||
| Line 29: | Line 38: | ||
[[Category: oxidoreductase]] | [[Category: oxidoreductase]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 13:33:58 2008'' |
Revision as of 11:33, 20 March 2008
| |||||||
| , resolution 2.60Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | and | ||||||
| Gene: | HOM6, YJR139C OR J2132 (Saccharomyces cerevisiae) | ||||||
| Activity: | Homoserine dehydrogenase, with EC number 1.1.1.3 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Homoserine Dehydrogenase in complex with suicide inhibitor complex NAD-5-hydroxy-4-Oxonorvaline
Overview
The structure of the antifungal drug 5-hydroxy-4-oxonorvaline (HON) in complex with its target homoserine dehydrogenase (HSD) has been determined by X-ray diffraction to 2.6 A resolution. HON shows potent in vitro and in vivo activity against various fungal pathogens despite its weak (2 mM) affinity for HSD in the steady state. The structure together with structure-activity relationship studies, mass spectrometry experiments, and spectroscopic data reveals that the molecular mechanism of antifungal action conferred by HON involves enzyme-dependent formation of a covalent adduct between C4 of the nicotinamide ring of NAD(+) and C5 of HON. Furthermore, novel interactions are involved in stabilizing the (HON*NAD)-adduct, which are not observed in the enzyme's ternary complex structure. These findings clarify the apparent paradox of the potent antifungal actions of HON given its weak steady-state inhibition characteristics.
About this Structure
1Q7G is a Single protein structure of sequence from Saccharomyces cerevisiae. Full crystallographic information is available from OCA.
Reference
Enzyme-assisted suicide: molecular basis for the antifungal activity of 5-hydroxy-4-oxonorvaline by potent inhibition of homoserine dehydrogenase., Jacques SL, Mirza IA, Ejim L, Koteva K, Hughes DW, Green K, Kinach R, Honek JF, Lai HK, Berghuis AM, Wright GD, Chem Biol. 2003 Oct;10(10):989-95. PMID:14583265
Page seeded by OCA on Thu Mar 20 13:33:58 2008
