1q7g

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[[Image:1q7g.gif|left|200px]]
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{{STRUCTURE_1q7g| PDB=1q7g | SCENE= }}
{{STRUCTURE_1q7g| PDB=1q7g | SCENE= }}
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'''Homoserine Dehydrogenase in complex with suicide inhibitor complex NAD-5-hydroxy-4-Oxonorvaline'''
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===Homoserine Dehydrogenase in complex with suicide inhibitor complex NAD-5-hydroxy-4-Oxonorvaline===
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==Overview==
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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.
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The line below this paragraph, {{ABSTRACT_PUBMED_14583265}}, adds the Publication Abstract to the page
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(as it appears on PubMed at http://www.pubmed.gov), where 14583265 is the PubMed ID number.
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{{ABSTRACT_PUBMED_14583265}}
==About this Structure==
==About this Structure==
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[[Category: Wright, G D.]]
[[Category: Wright, G D.]]
[[Category: Oxidoreductase]]
[[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 Tue Jul 29 14:53:25 2008''

Revision as of 11:53, 29 July 2008

Image:1q7g.png

Template:STRUCTURE 1q7g

Homoserine Dehydrogenase in complex with suicide inhibitor complex NAD-5-hydroxy-4-Oxonorvaline

Template:ABSTRACT PUBMED 14583265

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

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