1Q7G
Homoserine Dehydrogenase in complex with suicide inhibitor complex NAD-5-hydroxy-4-Oxonorvaline
Summary for 1Q7G
| Entry DOI | 10.2210/pdb1q7g/pdb |
| Descriptor | Homoserine dehydrogenase, SODIUM ION, NICOTINAMIDE-ADENINE-DINUCLEOTIDE-5-HYDROXY-4-OXONORVALINE, ... (4 entities in total) |
| Functional Keywords | oxidoreductase |
| Biological source | Saccharomyces cerevisiae (baker's yeast) |
| Total number of polymer chains | 2 |
| Total formula weight | 77945.45 |
| Authors | Jacques, S.L.,Mirza, I.A.,Ejim, L.,Koteva, K.,Hughes, D.W.,Green, K.,Kinach, R.,Honek, J.F.,Lai, H.K.,Berghuis, A.M.,Wright, G.D. (deposition date: 2003-08-18, release date: 2003-10-21, Last modification date: 2023-08-16) |
| Primary citation | Jacques, S.L.,Mirza, I.A.,Ejim, L.,Koteva, K.,Hughes, D.W.,Green, K.,Kinach, R.,Honek, J.F.,Lai, H.K.,Berghuis, A.M.,Wright, G.D. Enzyme assisted suicide: Molecular basis for the antifungal activity of 5-hydroxy-4-oxonorvaline by potent inhibition of homoserine dehydrogenase Chem.Biol., 10:989-995, 2003 Cited by PubMed Abstract: 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. PubMed: 14583265DOI: 10.1016/j.chembiol.2003.09.015 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.6 Å) |
Structure validation
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