| http://purl.uniprot.org/citations/14583265 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/14583265 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/14583265 | http://www.w3.org/2000/01/rdf-schema#comment | "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."xsd:string |
| http://purl.uniprot.org/citations/14583265 | http://purl.org/dc/terms/identifier | "doi:10.1016/j.chembiol.2003.09.015"xsd:string |
| http://purl.uniprot.org/citations/14583265 | http://purl.org/dc/terms/identifier | "doi:10.1016/j.chembiol.2003.09.015"xsd:string |
| http://purl.uniprot.org/citations/14583265 | http://purl.uniprot.org/core/author | "Berghuis A.M."xsd:string |
| http://purl.uniprot.org/citations/14583265 | http://purl.uniprot.org/core/author | "Berghuis A.M."xsd:string |
| http://purl.uniprot.org/citations/14583265 | http://purl.uniprot.org/core/author | "Wright G.D."xsd:string |
| http://purl.uniprot.org/citations/14583265 | http://purl.uniprot.org/core/author | "Wright G.D."xsd:string |
| http://purl.uniprot.org/citations/14583265 | http://purl.uniprot.org/core/author | "Hughes D.W."xsd:string |
| http://purl.uniprot.org/citations/14583265 | http://purl.uniprot.org/core/author | "Hughes D.W."xsd:string |
| http://purl.uniprot.org/citations/14583265 | http://purl.uniprot.org/core/author | "Honek J.F."xsd:string |
| http://purl.uniprot.org/citations/14583265 | http://purl.uniprot.org/core/author | "Honek J.F."xsd:string |
| http://purl.uniprot.org/citations/14583265 | http://purl.uniprot.org/core/author | "Ejim L."xsd:string |
| http://purl.uniprot.org/citations/14583265 | http://purl.uniprot.org/core/author | "Ejim L."xsd:string |
| http://purl.uniprot.org/citations/14583265 | http://purl.uniprot.org/core/author | "Green K."xsd:string |
| http://purl.uniprot.org/citations/14583265 | http://purl.uniprot.org/core/author | "Green K."xsd:string |
| http://purl.uniprot.org/citations/14583265 | http://purl.uniprot.org/core/author | "Jacques S.L."xsd:string |
| http://purl.uniprot.org/citations/14583265 | http://purl.uniprot.org/core/author | "Jacques S.L."xsd:string |
| http://purl.uniprot.org/citations/14583265 | http://purl.uniprot.org/core/author | "Kinach R."xsd:string |
| http://purl.uniprot.org/citations/14583265 | http://purl.uniprot.org/core/author | "Kinach R."xsd:string |
| http://purl.uniprot.org/citations/14583265 | http://purl.uniprot.org/core/author | "Koteva K."xsd:string |
| http://purl.uniprot.org/citations/14583265 | http://purl.uniprot.org/core/author | "Koteva K."xsd:string |
| http://purl.uniprot.org/citations/14583265 | http://purl.uniprot.org/core/author | "Lai H.K."xsd:string |
| http://purl.uniprot.org/citations/14583265 | http://purl.uniprot.org/core/author | "Lai H.K."xsd:string |