1q7g

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[[Image:1q7g.gif|left|200px]]
[[Image:1q7g.gif|left|200px]]
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{{Structure
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<!--
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|PDB= 1q7g |SIZE=350|CAPTION= <scene name='initialview01'>1q7g</scene>, resolution 2.60&Aring;
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The line below this paragraph, containing "STRUCTURE_1q7g", creates the "Structure Box" on the page.
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|SITE=
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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|LIGAND= <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NHO:NICOTINAMIDE-ADENINE-DINUCLEOTIDE-5-HYDROXY-4-OXONORVALINE'>NHO</scene>
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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|ACTIVITY= <span class='plainlinks'>[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] </span>
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or leave the SCENE parameter empty for the default display.
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|GENE= HOM6, YJR139C OR J2132 ([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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|DOMAIN=
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{{STRUCTURE_1q7g| PDB=1q7g | SCENE= }}
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|RELATEDENTRY=
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1q7g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1q7g OCA], [http://www.ebi.ac.uk/pdbsum/1q7g PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1q7g RCSB]</span>
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}}
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'''Homoserine Dehydrogenase in complex with suicide inhibitor complex NAD-5-hydroxy-4-Oxonorvaline'''
'''Homoserine Dehydrogenase in complex with suicide inhibitor complex NAD-5-hydroxy-4-Oxonorvaline'''
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[[Category: Mirza, I A.]]
[[Category: Mirza, I A.]]
[[Category: Wright, G D.]]
[[Category: Wright, G D.]]
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[[Category: oxidoreductase]]
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[[Category: Oxidoreductase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 05:57:46 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 23:09:49 2008''
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Revision as of 02:57, 3 May 2008

Image:1q7g.gif

Template:STRUCTURE 1q7g

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 Sat May 3 05:57:46 2008

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